Mechanisms of Rejection: Current Perspectives
Abstract
Rejection is the major barrier to successful transplantation. The immune response to an allograft is an ongoing dialogue between the innate and adaptive immune system that if left unchecked will lead to the rejection of transplanted cells, tissues, or organs. Activation of elements of the innate immune system, triggered as a consequence of tissue injury sustained during cell isolation or organ retrieval and ischemia reperfusion, will initiate and amplify the adaptive response. T cells require a minimum of two signals for activation, antigen recognition, and costimulation. The activation requirements of naive T cells are more stringent than those of memory T cells. Memory T cells are present in the majority of transplant recipients as a result of heterologous immunity. The majority of B cells require help from T cells to initiate antibody production. Antibodies reactive to donor human leukocyte antigen molecules, minor histocompatibility antigens, endothelial cells, RBCs, or autoantigens can trigger or contribute to rejection early and late after transplantation. Antibody-mediated rejection triggered by alloantibody binding and complement activation is recognized increasingly as a significant contribution to graft loss. Even though one component of the immune system may dominate and lead to rejection being described in short hand as T cell or antibody mediated, it is usually multifactorial resulting from the integration of multiple mechanisms. Identifying the molecular pathways that trigger tissue injury, signal transduction and rejection facilitates the identification of targets for the development of immunosuppressive drugs.
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Nuclear and mitochondrial DNA, ROS, and fragmented ECM components such as hyaluronic acid or fibronectin are among the most renowned DAMPs.
“Nuclear and mitochondrial DNA, reactive oxygen species (ROS), and fragmented ECM components such as hyaluronic acid or fibronectin are among the most renowned DAMPs, which are released due to perturbation in the arrangement of nucleic acids within cells, transplantation imperfections such as ischemia-reperfusion, and harsh decellularization strategies, respectively [34–37].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [34]
The interaction of dECM scaffolds with the innate immune system is mainly mediated via DAMPs, danger signals released upon cell and ECM damage during graft processing or implantation.
“The interaction of dECM scaffolds with the innate immune system is mainly mediated via damage-associated molecular patterns (DAMPs), danger signals released upon the cell and ECM damage during graft processing or implantation.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [34]
Innate immunity is insufficient for graft rejection, and its interplay with adaptive immunity determines graft fate.
“However, innate immunity is insufficient for graft rejection and immunological traits of the implant, and its interplay with adaptive immunity will determine its fate [34, 39, 43].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [34]
Cites
Pattern Recognition Receptors and Inflammation
Takeuchi, O., & Akira, S. (2010) · Cell · doi:10.1016/j.cell.2010.01.022 · Cited by 8,895 · see citing works
Greenwald, R. J., Freeman, G. J., & Sharpe, A. H. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115611 · Cited by 2,318 · see citing works
Up on the tightrope: natural killer cell activation and inhibition
Lanier, L. L. (2008) · Nature Immunology · doi:10.1038/ni1581 · Cited by 1,656 · see citing works
Regulatory T cells in transplantation tolerance
Wood, K. J., & Sakaguchi, S. (2003) · Nature reviews. Immunology · doi:10.1038/nri1027 · Cited by 1,318 · see citing works
Self-citationImmune cell migration in inflammation: present and future therapeutic targets
Luster, A. D., Alon, R., & von Andrian, U. H. (2005) · Nature Immunology · doi:10.1038/ni1275 · Cited by 1,313 · see citing works
Neutrophil kinetics in health and disease
Summers, C., Rankin, S. M., Condliffe, A. M., Singh, N., Peters, A. M., & Chilvers, E. R. (2010) · Trends in Immunology · doi:10.1016/j.it.2010.05.006 · Cited by 1,237 · see citing works
The complement system in regulation of adaptive immunity
Carroll, M. C. (2004) · Nature Immunology · doi:10.1038/ni1113 · Cited by 1,035 · see citing works
IL-10 Is Required for Regulatory T Cells to Mediate Tolerance to Alloantigens In Vivo
Hara, M., Kingsley, C. I., Niimi, M., Read, S., Turvey, S. E., Bushell, A., Morris, P. J., Powrie, F. M., & Wood, K. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.6.3789 · Cited by 765 · see citing works
Self-citationMolecular Heterogeneity in Acute Renal Allograft Rejection Identified by DNA Microarray Profiling
Sarwal, M., Chua, M., Kambham, N., Hsieh, S., Satterwhite, T. S., Masek, M., & Salvatierra, O. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa035588 · Cited by 698 · see citing works
Identification of a B cell signature associated with renal transplant tolerance in humans
Newell, K. A., Asare, A. L., Kirk, A. D., Gisler, T. D., Bourcier, K., Suthanthiran, M., Burlingham, W. J., Marks, W. H., Sanz, I., Lechler, R. I., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39933 · Cited by 676 · see citing works
Heterologous immunity provides a potent barrier to transplantation tolerance
Adams, A. B., Williams, M. A., Jones, T. R., Shirasugi, N., Durham, M. M., Kaech, S. M., Wherry, E. J., Onami, T. M., Lanier, J. G., Kokko, K. E., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17477 · Cited by 616 · see citing works
Rejection of the Kidney Allograft
Nankivell, B. J., & Alexander, S. I. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0902927 · Cited by 605 · see citing works
Larsen, C. P., Morris, P. J., & Austyn, J. M. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.171.1.307 · Cited by 561 · see citing works
Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans
Sagoo, P., Perucha, E., Sawitzki, B., Tomiuk, S., Stephens, D. A., Miqueu, P., Chapman, S. J., Craciun, L., Sergeant, R., Brouard, S., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39922 · Cited by 527 · see citing works
Self-citationAntibody-mediated organ-allograft rejection
Colvin, R. B., & Smith, R. N. (2005) · Nature reviews. Immunology · doi:10.1038/nri1702 · Cited by 494 · see citing works
The Inflammasome: First Line of the Immune Response to Cell Stress
Ogura, Y., Sutterwala, F. S., & Flavell, R. A. (2006) · Cell · doi:10.1016/j.cell.2006.08.002 · Cited by 474 · see citing works
B cell follicles and antigen encounters of the third kind
Cyster, J. G. (2010) · Nature Immunology · doi:10.1038/ni.1946 · Cited by 342 · see citing works
A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy
Yuan, X., Paez-Cortez, J. R., Schmitt-Knosalla, I., D’Addio, F., Mfarrej, B. G., Donnarumma, M., Habicht, A., Clarkson, M. R., Iacomini, J., Glimcher, L. H., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20081937 · Cited by 302 · see citing works
Human Leukocyte Antigen Antibodies and Chronic Rejection: From Association to Causation
Terasaki, P. I., & Cai, J. (2008) · Transplantation · doi:10.1097/tp.0b013e31817c4cb8 · Cited by 246 · see citing works
Costimulatory pathways in transplantation: challenges and new developments
Li, X. C., Rothstein, D. M., & Sayegh, M. H. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00781.x · Cited by 197 · see citing works
Cai, J., & Terasaki, P. I. (2010) · Transplantation · doi:10.1097/tp.0b013e3181fecfcb · Cited by 166 · see citing works
MicroRNAs: Small RNAs With Big Effects
Anglicheau, D., Muthukumar, T., & Suthanthiran, M. (2010) · Transplantation · doi:10.1097/tp.0b013e3181e913c2 · Cited by 165 · see citing works
Pathways of major histocompatibility complex allorecognition
Afzali, B., Lombardi, G., & Lechler, R. I. (2008) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e328309ee31 · Cited by 165 · see citing works
The Changing Role of Natural Killer Cells in Solid Organ Rejection and Tolerance
Kitchens, W. H., Uehara, S., Chase, C. M., Colvin, R. B., Russell, P. S., & Madsen, J. C. (2006) · Transplantation · doi:10.1097/01.tp.0000202844.33794.0e · Cited by 140 · see citing works
Macrophage Depletion Suppresses Cardiac Allograft Vasculopathy in Mice
Kitchens, W. H., Chase, C. M., Uehara, S., Cornell, L. D., Colvin, R. B., Russell, P. S., & Madsen, J. C. (2007) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2007.01997.x · Cited by 132 · see citing works
Texier, L. L., Thébault, P., Lavault, A., Usal, C., Mérieau, E., Quillard, T., Charreau, B. L., Soulillou, J. P., Cuturi, M. C., Brouard, S., et al. (2010) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2010.03336.x · Cited by 130 · see citing works
The Value of Machine Perfusion Perfusate Biomarkers for Predicting Kidney Transplant Outcome
Moers, C., Varnav, O. C., van Heurn, E. L. W., Jochmans, I., Kirste, G. R., Rahmel, A. O., Leuvenink, H. G. D., Squifflet, J., Paul, A., Pirenne, J., et al. (2010) · Transplantation · doi:10.1097/tp.0b013e3181f5c40c · Cited by 129 · see citing works
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Heidt, S., San, D., Chadha, R., & Wood, K. J. (2010) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e32833b9bfb · Cited by 112 · see citing works
Self-citationThe Impact of Memory T Cells on Rejection and the Induction of Tolerance
Brook, M. O., Wood, K. J., & Jones, N. D. (2006) · Transplantation · doi:10.1097/01.tp.0000226082.17507.da · Cited by 108 · see citing works
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Anglicheau, D., & Suthanthiran, M. (2008) · Transplantation · doi:10.1097/tp.0b013e31817eef7b · Cited by 104 · see citing works
The relevance of minor histocompatibility antigens in solid organ transplantation
Dierselhuis, M. P., & Goulmy, E. (2009) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e32832d399c · Cited by 88 · see citing works
Transcriptome Analysis Reveals Heterogeneity in the Injury Response of Kidney Transplants
Famulski, K. S., Broderick, G., Einecke, G., Hay, K., Cruz, J., Sis, B., Mengel, M., & Halloran, P. F. (2007) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2007.01980.x · Cited by 83 · see citing works
Dendritic Cells as a Tool to Induce Transplantation Tolerance: Obstacles and Opportunities
van Kooten, C., Lombardi, G., Gelderman, K. A., Sagoo, P., Buckland, M. S., Lechler, R. I., & Cuturi, M. C. (2010) · Transplantation · doi:10.1097/tp.0b013e31820263b3 · Cited by 77 · see citing works
Chadha, R., Heidt, S., Jones, N. D., & Wood, K. J. (2011) · Transplantation · doi:10.1097/tp.0b013e3182126eeb · Cited by 75 · see citing works
Self-citationTo B or not to B: a question of resolution?
Merritt, E. A. (2012) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444911028320 · Cited by 75 · see citing works
Impact of Innate and Adaptive Immunity on Rejection and Tolerance
Kim, I. K., Bedi, D. S., Denecke, C., Ge, X., & Tullius, S. G. (2008) · Transplantation · doi:10.1097/tp.0b013e318186ac4a · Cited by 74 · see citing works
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Lo, D. J., Weaver, T. A., Kleiner, D. E., Mannon, R. B., Jacobson, L. M., Becker, B. N., Swanson, S. J., Hale, D. A., & Kirk, A. D. (2010) · Transplantation · doi:10.1097/tp.0b013e3181fe12fc · Cited by 72 · see citing works
Regulatory T Cells in Transplantation: Transferring Mouse Studies to the Clinic
Long, E., & Wood, K. J. (2009) · Transplantation · doi:10.1097/tp.0b013e3181bb7913 · Cited by 72 · see citing works
Self-citationFaust, S. M., Lu, G., Marini, B. L., Zou, W., Gordon, D., Iwakura, Y., Laouar, Y., & Bishop, D. K. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0902446 · Cited by 70 · see citing works
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Hosgood, S. A., & Nicholson, M. L. (2010) · Transplantation · doi:10.1097/tp.0b013e3181da6064 · Cited by 64 · see citing works
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Asgari, E., Zhou, W., & Sacks, S. H. (2010) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e32833b9cb7 · Cited by 62 · see citing works
Interleukin-23 and Th17 Cells in Transplantation Immunity: Does 23+17 Equal Rejection?
Chen, Y., & Wood, K. J. (2007) · Transplantation · doi:10.1097/01.tp.0000287126.12083.48 · Cited by 60 · see citing works
Self-citationBoyd, A. S., Higashi, Y., & WOOD, K. (2005) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2005.08.004 · Cited by 57 · see citing works
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Zarkhin, V., Li, L., & Sarwal, M. (2008) · Transplantation · doi:10.1097/tp.0b013e318177793e · Cited by 57 · see citing works
The role of H-2 and non-H-2 antigens and genes in the rejection of murine cardiac allografts
PEUGH, W. N., Superina, R. A., Wood, K. J., & Morris, P. J. (1986) · Immunogenetics · doi:10.1007/bf00376519 · Cited by 53 · see citing works
Self-citationHumoral Autoimmunity and Transplant Vasculopathy: When Allo is Not Enough
Win, T. S., & Pettigrew, G. J. (2010) · Transplantation · doi:10.1097/tp.0b013e3181e25a59 · Cited by 51 · see citing works
Pathophysiologic Significance of B-Cell Clusters in Chronically Rejected Grafts
Thaunat, O. (2011) · Transplantation · doi:10.1097/tp.0b013e31821f74fe · Cited by 50 · see citing works
Bedi, D. S., Riella, L. V., Tullius, S. G., & Chandraker, A. K. (2010) · Transplantation · doi:10.1097/tp.0b013e3181efcfbc · Cited by 50 · see citing works
Barbara, J. A. J., Turvey, S. E., Kingsley, C. I., Spriewald, B. M., Hara, M., Witzke, O., Morris, P. J., & Wood, K. J. (2000) · Transplantation · doi:10.1097/00007890-200012150-00017 · Cited by 50 · see citing works
Self-citationScheepstra, C. G., Bemelman, F. J., van der Loos, C. M., Rowshani, A. T., der Pant, K. A. M. I. V. D., Idu, M. M., ten Berge, I. J. M., & Florquin, S. (2008) · Transplantation · doi:10.1097/tp.0b013e3181860a74 · Cited by 48 · see citing works
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Bouma, H. R., Ketelaar, M. E., Yard, B. A., Ploeg, R. J., & Henning, R. H. (2010) · Transplantation · doi:10.1097/tp.0b013e3181e7a3aa · Cited by 47 · see citing works
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Pallet, N., Fougeray, S., Beaune, P. H., Legendre, C. M., Thervet, É., & Anglicheau, D. (2009) · Transplantation · doi:10.1097/tp.0b013e3181b22cec · Cited by 47 · see citing works
Chemokine gene expression during allograft rejection: Comparison of two quantitative PCR techniques
Carvalho‐Gaspar, M., Billing, J. S., Spriewald, B. M., & Wood, K. J. (2005) · Journal of Immunological Methods · doi:10.1016/j.jim.2005.03.003 · Cited by 46 · see citing works
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Naesens, M., Zarkhin, V., Kambham, N., Li, L., Kwok, S., Hsieh, S.-J. J., Salvatierra, O., & Sarwal, M. (2008) · Transplantation · doi:10.1097/01.tp.0000332191.92932.c7 · Cited by 2 · see citing works
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Motallebzadeh, R., Rehakova, S., Goddard, M. J., Negus, M. C., Bolton, E. M., Ruddle, N. H., Bradley, J. A., & Pettigrew, G. J. (2010) · Transplantation · doi:10.1097/00007890-201007272-00899 · Cited by 2 · see citing works
Tan, H. P., Chaudhary, A., Humar, A., DONALDSON, J., Basu, A., Morgan, C., Unruh, M. L., McCauley, J., Wu, C., Shah, N., et al. (2010) · Transplantation · doi:10.1097/00007890-201007272-00336 · Cited by 1 · see citing works
Flagged first, then by citations
1 of the 65 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Kim, C. J., Romero, R. J., Chaemsaithong, P., & Kim, J.-S. (2015) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2015.08.041 · Cited by 520 · see citing works
Advances in Regenerative Medicine and Tissue Engineering: Innovation and Transformation of Medicine
Dzobo, K., Thomford, N. E., Senthebane, D. A., Shipanga, H., Rowe, A., Dandara, C., Pillay, M., & Motaung, K. S. (2018) · Stem Cells International · doi:10.1155/2018/2495848 · Cited by 455 · see citing works
Regulatory immune cells in transplantation
Wood, K. J., Bushell, A., & Hester, J. (2012) · Nature reviews. Immunology · doi:10.1038/nri3227 · Cited by 433 · see citing works
Self-citationKasravi, M., Ahmadi, A., Babajani, A., Mazloomnejad, R., Hatamnejad, M. R., Shariatzadeh, S., Bahrami, S., & Niknejad, H. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00348-z · Cited by 316 · see citing works
Immunogenicity in xenogeneic scaffold generation: Antigen removal vs. decellularization
Wong, M. L., & Griffiths, L. G. (2014) · Acta Biomaterialia · doi:10.1016/j.actbio.2014.01.028 · Cited by 254 · see citing works
Griffin, M. D., Ryan, A. E., Alagesan, S., Lohan, P., Treacy, O., & Ritter, T. (2012) · Immunology and Cell Biology · doi:10.1038/icb.2012.67 · Cited by 250 · see citing works
Streitz, M., Miloud, T., Kapinsky, M., Reed, M. R., Magari, R. T., Geissler, E. K., Hutchinson, J. A., Vogt, K., Schlickeiser, S., Kverneland, A. H., et al. (2013) · Transplantation Research · doi:10.1186/2047-1440-2-17 · Cited by 215 · see citing works
Origin and Consequences of Necroinflammation
Sarhan, M., Land, W. G., Tonnus, W., Hugo, C., & Linkermann, A. (2018) · Physiological Reviews · doi:10.1152/physrev.00041.2016 · Cited by 210 · see citing works
Abu-Elmagd, K. M., Kosmach‐Park, B., Costa, G., Zenati, M. S., Martin, L., Koritsky, D. A., Emerling, M., Murase, N., Bond, G. J., Soltys, K. A., et al. (2012) · Annals of Surgery · doi:10.1097/sla.0b013e318265f310 · Cited by 208 · see citing works
Abu-Elmagd, K. M., Wu, G. S., Costa, G., Lunz, J. G., Martin, L., Koritsky, D. A., Murase, N., Irish, W. D., & Zeevi, A. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2012.04237.x · Cited by 200 · see citing works
From immunosuppression to tolerance
Adams, D., Fueyo, A. S., & Samuel, D. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.042 · Cited by 182 · see citing works
Transplantation and Damage-Associated Molecular Patterns (DAMPs)
Land, W. G., Agostinis, P., Gasser, S., Garg, A. D., & Linkermann, A. (2016) · American Journal of Transplantation · doi:10.1111/ajt.13963 · Cited by 166 · see citing works
Sivanathan, K. N., Gronthos, S., Rojas‐Canales, D. M., Thierry, B., & Coates, P. T. (2014) · Stem Cell Reviews and Reports · doi:10.1007/s12015-014-9495-2 · Cited by 156 · see citing works
Mesenchymal stromal cells in renal transplantation: opportunities and challenges
Casiraghi, F., Perico, N., Cortinovis, M., & Remuzzi, G. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.7 · Cited by 152 · see citing works
Kwun, J., Matignon, M., Manook, M., Guendouz, S., Audard, V., Kheav, V., Poullot, E., Gautreau, C., Ezekian, B., Bodez, D., et al. (2019) · Journal of the American Society of Nephrology · doi:10.1681/asn.2018121254 · Cited by 140 · see citing works
Engineering the Surface of Therapeutic “Living” Cells
Park, J., Andrade, B., Seo, Y., Kim, M., Zimmerman, S. C., & Kong, H. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00157 · Cited by 140 · see citing works
Nilsson, J., Jernryd, V., Qin, G., Paskevicius, A., Metzsch, C., Sjöberg, T., & Steen, S. (2020) · Nature Communications · doi:10.1038/s41467-020-16782-9 · Cited by 130 · see citing works
Heidt, S., Hester, J., Shankar, S., Friend, P. J., & Wood, K. J. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2012.04012.x · Cited by 126 · see citing works
Self-citationLiu, J. M.-H., Zhang, J., Zhang, X., Hlavaty, K. A., Ricci, C. F., Leonard, J. N., Shea, L. D., & Gower, R. M. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.11.065 · Cited by 119 · see citing works
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Mac, Q. D., Mathews, D., Kahla, J. A., Stoffers, C. M., Delmas, O. M., Holt, B. A., Adams, A. B., & Kwong, G. A. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0358-7 · Cited by 120 · see citing works
Li, X., Li, J., Yang, J., Wang, D., Zhao, W., Song, W., Li, W., Wang, J.-F., Han, W., Zhang, Z., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044045 · Cited by 118 · see citing works
Dixit, S., Baganizi, D. R., Sahu, R., Dosunmu, E., Chaudhari, A. A., Vig, K., Pillai, S., Singh, S. R., & Dennis, V. A. (2017) · Journal of Biological Engineering · doi:10.1186/s13036-017-0089-9 · Cited by 118 · see citing works
Arzi, B., Clark, K. C., Sundaram, A., Spriet, M. P., Verstraete, F. J. Μ., Walker, N. J., Loscar, M. R., Fazel, N., Murphy, W. J., Vapniarsky, N., et al. (2017) · Stem Cells Translational Medicine · doi:10.1002/sctm.17-0035 · Cited by 110 · see citing works
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Self-citationMescher, A. L., Neff, A. W., & King, M. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080477 · Cited by 85 · see citing works
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Eikmans, M., Gielis, E. M., Ledeganck, K. J., Yang, J., Abramowicz, D., & Claas, F. H. J. (2019) · Frontiers in Medicine · doi:10.3389/fmed.2018.00358 · Cited by 86 · see citing works
Three dimensional printed nanostructure biomaterials for bone tissue engineering
Marew, T., & Birhanu, G. (2021) · Regenerative Therapy · doi:10.1016/j.reth.2021.05.001 · Cited by 83 · see citing works
Kinnear, G., Jones, N. D., & Wood, K. J. (2012) · Transplantation · doi:10.1097/tp.0b013e31826d4672 · Cited by 82 · see citing works
Self-citationMesenchymal Stromal Cells for Transplant Tolerance
Podestà, M. A., Remuzzi, G., & Casiraghi, F. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01287 · Cited by 82 · see citing works
Sarhane, K. A., TUFFAHA, S. H., Broyles, J. M., Ibrahim, A. E., Khalifian, S., Baltodano, P. A., Santiago, G. F., Alrakan, M., & Ibrahim, Z. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00406 · Cited by 81 · see citing works
Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies
Alelign, T., Ahmed, M. M., Bobosha, K., Tadesse, Y., Howe, R., & Petros, B. (2018) · Journal of Immunology Research · doi:10.1155/2018/5986740 · Cited by 79 · see citing works
Gower, R. M., Boehler, R. M., Azarin, S. M., Ricci, C. F., Leonard, J. N., & Shea, L. D. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.036 · Cited by 78 · see citing works
Immunogenicity of Allogeneic Mesenchymal Stromal Cells: What Has Been Seen in Vitro and in Vivo ?
Consentius, C., Reinke, P., & Volk, H. (2015) · Regenerative Medicine · doi:10.2217/rme.15.14 · Cited by 78 · see citing works
Ono, M., Oshima, M., Ogawa, M., Sonoyama, W., Hara, E. S., Oida, Y., Shinkawa, S., Nakajima, R., Mine, A., Hayano, S., et al. (2017) · Scientific Reports · doi:10.1038/srep44522 · Cited by 75 · see citing works
Lohan, P., Coleman, C. M., Murphy, M. J., Griffin, M. D., Ritter, T., & Ryan, A. E. (2014) · Stem Cell Research & Therapy · doi:10.1186/scrt488 · Cited by 76 · see citing works
mTOR inhibitors effects on regulatory T cells and on dendritic cells
Stallone, G., Infante, B., Lorenzo, A. D., Rascio, F., Zaza, G., & Grandaliano, G. (2016) · Journal of Translational Medicine · doi:10.1186/s12967-016-0916-7 · Cited by 76 · see citing works
Human monocytes produce interferon-gamma upon stimulation with LPS
Kraaij, M. D., Vereyken, E. J. F., Leenen, P. J. M., van den Bosch, T. P. P., Rezaee, F., Betjes, M. G. H., Baan, C. C., & Rowshani, A. T. (2014) · Cytokine · doi:10.1016/j.cyto.2014.02.001 · Cited by 71 · see citing works
Cardiac transplantation: indications, eligibility and current outcomes
Bhagra, S. K., Pettit, S., & Parameshwar, J. K. (2018) · Heart · doi:10.1136/heartjnl-2018-313103 · Cited by 70 · see citing works
CXCL 10 and IL ‐6: Markers of two different forms of intra‐amniotic inflammation in preterm labor
Romero, R. J., Chaemsaithong, P., Chaiyasit, N., Docheva, N., Dong, Z., Kim, C. J., Kim, Y. M., Kim, J.-S., Qureshi, F., Jacques, S. M., et al. (2017) · American Journal of Reproductive Immunology · doi:10.1111/aji.12685 · Cited by 70 · see citing works
Figueiredo, C., Oliveira, M. C., Chen, C., Jansson, K., Höffler, K., Yuzefovych, Y., Pogozhykh, O., Jin, Z., Kühnel, M., Jonigk, D. D., et al. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.117 · Cited by 69 · see citing works
IL-34 Inhibits Acute Rejection of Rat Liver Transplantation by Inducing Kupffer Cell M2 Polarization
Zhao, Z., Pan, G., Tang, C., Li, Z., Zheng, D., Wei, X., & Wu, Z. (2018) · Transplantation · doi:10.1097/tp.0000000000002194 · Cited by 67 · see citing works
B Cell Immunity in Solid Organ Transplantation
Karahan, G. E., Claas, F. H. J., & Heidt, S. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00686 · Cited by 66 · see citing works
Matching for Human Leukocyte Antigens (HLA) in corneal transplantation – To do or not to do
van Essen, T. H., Roelen, D. L., Williams, K. A., & Jager, M. J. (2015) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.01.001 · Cited by 65 · see citing works
Effect of Angiogenesis in Bone Tissue Engineering
Huang, J., Han, Q., Cai, M., Zhu, J., Li, L., Yu, L., Wang, Z., Fan, G., Zhu, Y., Lü, J., et al. (2022) · Annals of Biomedical Engineering · doi:10.1007/s10439-022-02970-9 · Cited by 64 · see citing works
Li, L., Wang, R., Jia, Y., Rong, R., Xu, M., & Zhu, T. (2019) · Frontiers in Medicine · doi:10.3389/fmed.2019.00269 · Cited by 60 · see citing works
Endothelial Injury in Renal Antibody-Mediated Allograft Rejection
Drachenberg, C. B., & Papadimitriou, J. C. (2013) · Transplantation · doi:10.1097/tp.0b013e31827e6b45 · Cited by 60 · see citing works
Immune response associated with ischemia and reperfusion injury during organ transplantation
Tang, Q., Dong, C., & Sun, Q. (2022) · Inflammation Research · doi:10.1007/s00011-022-01651-6 · Cited by 59 · see citing works
Understanding Stem Cell Immunogenicity in Therapeutic Applications
Wood, K. J., Issa, F., & Hester, J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.11.005 · Cited by 59 · see citing works
Self-citationNaji, A., Rouas‐Freiss, N., Dürrbach, A., Carosella, E. D., Sensebé, L., & Deschaseaux, F. (2013) · Stem Cells · doi:10.1002/stem.1494 · Cited by 58 · see citing works
Exome Sequencing and Prediction of Long-Term Kidney Allograft Function
Mesnard, L., Muthukumar, T., Burbach, M., Li, C. Y., Shang, H., Dadhania, D. M., Lee, J. R., Sharma, V. K., Xiang, J., Suberbielle, C., et al. (2016) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1005088 · Cited by 58 · see citing works
The mechanisms of rejection in solid organ transplantation
Cozzi, E., Colpo, A., & De Silvestro, G. (2017) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2017.07.005 · Cited by 57 · see citing works
B cells with immune-regulating function in transplantation
Stolp, J., Turka, L., & Wood, K. (2014) · Nature Reviews Nephrology · doi:10.1038/nrneph.2014.80 · Cited by 61 · see citing works
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Elsabbagh, A. M., Hawksworth, J. S., Khan, K., Kaufman, S. S., Yazigi, N. A., Kroemer, A., Smith, C. I., Fishbein, T., & Matsumoto, C. (2019) · American Journal of Transplantation · doi:10.1111/ajt.15269 · Cited by 56 · see citing works
Freeley, M., & Long, A. (2013) · Biochemical Journal · doi:10.1042/bj20130950 · Cited by 54 · see citing works
Dollinger, B. R., Gupta, M. K., Martin, J. R., & Duvall, C. L. (2017) · Tissue Engineering Part A · doi:10.1089/ten.tea.2016.0495 · Cited by 51 · see citing works
Kanitakis, J., Karayannopoulou, G., Lanzetta, M., & Petruzzo, P. (2014) · Transplant International · doi:10.1111/tri.12399 · Cited by 50 · see citing works
Supplemental mineral ions for bone regeneration and osteoporosis treatment
Su, Y., Cappock, M., Dobres, S., Kucine, A. J., Waltzer, W. C., & Zhu, D. (2023) · Engineered Regeneration · doi:10.1016/j.engreg.2023.02.003 · Cited by 50 · see citing works
Mechanisms of rejection in vascular composite allotransplantation
Etra, J. W., Raimondi, G., & Brandacher, G. (2017) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0000000000000490 · Cited by 49 · see citing works
Chandrasekharan, D. P., Issa, F., & Wood, K. J. (2013) · Transplant International · doi:10.1111/tri.12081 · Cited by 47 · see citing works
Self-citationLei, T., Chen, L., Wang, K., Du, S., Gonelle‐Gispert, C., Wang, Y., & Bühler, L. H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1031185 · Cited by 44 · see citing works
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Stolp, J., Zaitsu, M., & Wood, K. J. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-8938-6_12 · Cited by 44 · see citing works
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Vlahos, A. E., Talior‐Volodarsky, I., Kinney, S. M., & Sefton, M. V. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120499 · Cited by 44 · see citing works
Hoffmann, U., Neudörfl, C., Daemen, K., Keil, J., Stevanovic-Meyer, M., Lehner, F., Haller, H. G., Blume, C. A., & Falk, C. S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0132484 · Cited by 44 · see citing works
Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ
Uehara, M., McGrath, M. M., Ohori, S., Solhjou, Z., Banouni, N., Routray, S. K., Evans, C. A., DiNitto, J. P., Elkhal, A., Turka, L. A., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00982-x · Cited by 43 · see citing works
Goto, R., You, S., Zaitsu, M., Chatenoud, L., & Wood, K. J. (2013) · American Journal of Transplantation · doi:10.1111/ajt.12272 · Cited by 42 · see citing works
Self-citationGraft microvascular disease in solid organ transplantation
Jiang, X., Sung, Y. K., Tian, W., Qian, J., Semenza, G. L., & Nicolls, M. R. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-014-1173-y · Cited by 42 · see citing works
The influence of ischemia and reperfusion time on outcome in heart transplantation
Jernryd, V., Metzsch, C., Andersson, B., & Nilsson, J. (2020) · Clinical Transplantation · doi:10.1111/ctr.13840 · Cited by 42 · see citing works
Gajardo, T., Morales, R. A., Campos‐Mora, M., Campos‐Acuña, J., & Pino‐Lagos, K. (2015) · Immunology · doi:10.1111/imm.12483 · Cited by 41 · see citing works
Myeloid-Derived Suppressor Cells as a Regulator of Immunity in Organ Transplantation
Nakamura, T., & Ushigome, H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082357 · Cited by 41 · see citing works
Gu, H., Xie, M., Xu, L., Zheng, X., Yang, Y., & Lv, X. (2015) · Transplant International · doi:10.1111/tri.12683 · Cited by 40 · see citing works
Update on lung transplantation: programmes, patients and prospects
Kotsimbos, T. C., Williams, T. J., & Anderson, G. P. (2012) · European Respiratory Review · doi:10.1183/09059180.00006312 · Cited by 40 · see citing works
Murine animal models for preclinical islet transplantation
Cantarelli, E., Citro, A., Marzorati, S., Melzi, R., Scavini, M., & Piemonti, L. (2013) · Islets · doi:10.4161/isl.24698 · Cited by 40 · see citing works
Dermal Papilla Cells: From Basic Research to Translational Applications
Zhang, H.-L., Qiu, X.-X., & Liao, X. (2024) · Biology · doi:10.3390/biology13100842 · Cited by 39 · see citing works
Effects of Metalloporphyrins on Reducing Inflammation and Autoimmunity
Delmastro-Greenwood, M. M., Tse, H. M., & Piganelli, J. D. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5257 · Cited by 39 · see citing works
Role of mesenchymal stem cell-derived exosomes in the regeneration of different tissues
Huang, D., Shen, H., Xie, F., Hu, D., Jin, Q., Hu, Y., & Zhong, T. (2024) · Journal of Biological Engineering · doi:10.1186/s13036-024-00431-6 · Cited by 39 · see citing works
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Self-citationPonticelli, C. E., & Campise, M. (2021) · Kidney International · doi:10.1016/j.kint.2021.04.016 · Cited by 38 · see citing works
Hyperlipidemia Promotes Anti-Donor Th17 Responses That Accelerate Allograft Rejection
Yuan, J., Bagley, J., & Iacomini, J. (2015) · American Journal of Transplantation · doi:10.1111/ajt.13350 · Cited by 37 · see citing works
Kollár, B., Kamat, P., Klein, H. J., Waldner, M., Schweizer, R., & Plock, J. A. (2019) · Journal of Vascular Research · doi:10.1159/000500958 · Cited by 37 · see citing works
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Wu, P., Xi, X., Li, R., & Sun, G. (2021) · Macromolecular Bioscience · doi:10.1002/mabi.202100141 · Cited by 37 · see citing works
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Issa, F., Robb, R. J., & Wood, K. J. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.11.003 · Cited by 36 · see citing works
Self-citationFindeisen, K., Morticelli, L., Goecke, T., Kolbeck, L., Ramm, R., Höffler, H., Brandes, G., Korossis, S., Haverich, A., & Hilfiker, A. (2020) · Xenotransplantation · doi:10.1111/xen.12617 · Cited by 36 · see citing works
Vascularized composite allograft-specific characteristics of immune responses
Issa, F. (2016) · Transplant International · doi:10.1111/tri.12765 · Cited by 36 · see citing works
Borges, T. J., O’Malley, J. T., Wo, L. M., Murakami, N., Smith, B., Azzi, J. R., Tripathi, S., Lane, J. D., Bueno, E. M., Clark, R. A., et al. (2016) · American Journal of Transplantation · doi:10.1111/ajt.13705 · Cited by 35 · see citing works
Thaunat, O., Badet, L., Dubois, V., Kanitakis, J., Petruzzo, P., & Morélon, E. (2015) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0000000000000242 · Cited by 35 · see citing works
Clopidogrel significantly lowers the development of atherosclerosis in ApoE-deficient mice in vivo
Heim, C., Gebhardt, J., Ramsperger-Gleixner, M., Jacobi, J., Weyand, M., & Ensminger, S. M. (2015) · Heart and Vessels · doi:10.1007/s00380-015-0696-7 · Cited by 35 · see citing works
Vereyken, E. J. F., Kraaij, M. D., Baan, C. C., Rezaee, F., Weimar, W., Wood, K. J., Leenen, P. J. M., & Rowshani, A. T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070152 · Cited by 33 · see citing works
Self-citationTranslating tolerogenic therapies to the clinic – where do we stand?
Issa, F., & Wood, K. J. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00254 · Cited by 33 · see citing works
Self-citationHeidt, S., Vergunst, M., Anholts, J. D. H., Reinders, M. E. J., de Fijter, J. W., Eikmans, M., & Claas, F. H. J. (2014) · Transplantation · doi:10.1097/tp.0000000000000465 · Cited by 33 · see citing works
Small Extracellular Vesicles in Transplant Rejection
Gołębiewska, J., Wardowska, A., Pietrowska, M., Wojakowska, A., & Dębska-Ślizień, A. M. (2021) · Cells · doi:10.3390/cells10112989 · Cited by 33 · see citing works
Mbughuni, M. M., Stevens, M. A., Langman, L. J., Kudva, Y. C., Sánchez, W., Dean, P. G., & Jannetto, P. J. (2020) · The Journal of Applied Laboratory Medicine · doi:10.1093/jalm/jfaa005 · Cited by 32 · see citing works
Late acute rejection: Incidence, risk factors, and effect on graft survival and function
Eid, L., Tuchman, S., & Moudgil, A. (2013) · Pediatric Transplantation · doi:10.1111/petr.12203 · Cited by 32 · see citing works
Lohan, P., Treacy, O., Lynch, K., Barry, F., Murphy, M. J., Griffin, M. D., Ritter, T., & Ryan, A. E. (2015) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2015.10.005 · Cited by 31 · see citing works
Wan, Y., Yu, Y., Yu, C., Luo, J., Wen, S., Shen, L., Wei, G., & Hua, Y. (2023) · Renal Failure · doi:10.1080/0886022x.2023.2221138 · Cited by 31 · see citing works
Bagley, J., Yuan, J., Chandrakar, A., & Iacomini, J. (2015) · American Journal of Transplantation · doi:10.1111/ajt.13351 · Cited by 31 · see citing works
A review of the immune response stimulated by xenogenic tissue heart valves
Bozso, S. J., EL‐Andari, R., Al‐Adra, D. P., Moon, M. C., Freed, D. H., Nagendran, J., & Nagendran, J. (2020) · Scandinavian Journal of Immunology · doi:10.1111/sji.13018 · Cited by 30 · see citing works
Targeting CD8 T-Cell Metabolism in Transplantation
Yap, M., Brouard, S., Pecqueur, C., & Degauque, N. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00547 · Cited by 29 · see citing works
Biomarkers and possible mechanisms of operational tolerance in kidney transplant patients
Dugast, E., Chesneau, M., Soulillou, J., & Brouard, S. (2014) · Immunological Reviews · doi:10.1111/imr.12156 · Cited by 29 · see citing works
HLA‐G dimer targets Granzyme B pathway to prolong human renal allograft survival
Ajith, A., Portik‐Dobos, V., Nguyen‐Lefebvre, A. T., Callaway, C., Horuzsko, D. D., Kapoor, R., Zayas, C. F., Maenaka, K., Mulloy, L. L., & Horuzsko, A. (2019) · The FASEB Journal · doi:10.1096/fj.201802017r · Cited by 29 · see citing works
- Authors
- Wood, K. J., & Goto, R.
- Affiliations
- John Radcliffe Hospital (GB)
- Corresponding author
- Wood, Kathryn J.
- ORCID
- Goto, Ryoichi
- Venue
- Transplantation
- Published
- 2012-01-15
- Volume
- 93
- Issue
- 1
- Pages
- 1-10
- ISSN
- 0041-1337 (ISSN-L)
- OpenAlex
- W1973175840
- Cited by
- 369
- References
- 65
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 18 · 2023: 19 · 2022: 14 · 2021: 22 · 2020: 25 · 2019: 24 · 2018: 27 · 2017: 27 · 2016: 25 · 2015: 36 · 2014: 43 · 2013: 32 · 2012: 31
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Transplantation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- British Heart Foundation
- Topics
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Keywords
- graft rejection, innate immune activation, adaptive immune response, T cell activation, costimulation, memory T cells, heterologous immunity, B cell help, antibody-mediated rejection, alloantibodies, complement activation, minor histocompatibility antigens, HLA antibodies, ischemia-reperfusion injury, graft loss
- MeSH terms
- B-Lymphocytes, Graft Rejection, Humans, Immunity, Innate, T-Lymphocytes, Signal Transduction, Organ Transplantation
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