T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection

McKinney, Eoin F.; Lee, James C.; Jayne, David R. W.; Lyons, Paul A.; Smith, Kenneth G. C.

doi:10.1038/nature14468

Cited by 692T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersDiabetes and associated disorders

T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection

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McKinney, Eoin F., Lee, James C., Jayne, David R. W., Lyons, Paul A., Smith, Kenneth G. C.·2015·Nature

DOI 10.1038/nature14468PMC PMC4623162

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Abstract

The clinical course of autoimmune and infectious disease varies greatly, even between individuals with the same condition. An understanding of the molecular basis for this heterogeneity could lead to significant improvements in both monitoring and treatment. During chronic infection the process of T-cell exhaustion inhibits the immune response, facilitating viral persistence. Here we show that a transcriptional signature reflecting CD8 T-cell exhaustion is associated with poor clearance of chronic viral infection, but conversely predicts better prognosis in multiple autoimmune diseases. The development of CD8 T-cell exhaustion during chronic infection is driven both by persistence of antigen and by a lack of accessory 'help' signals. In autoimmunity, we find that where evidence of CD4 T-cell co-stimulation is pronounced, that of CD8 T-cell exhaustion is reduced. We can reproduce the exhaustion signature by modifying the balance of persistent stimulation of T-cell antigen receptors and specific CD2-induced co-stimulation provided to human CD8 T cells in vitro, suggesting that each process plays a role in dictating outcome in autoimmune disease. The 'non-exhausted' T-cell state driven by CD2-induced co-stimulation is reduced by signals through the exhaustion-associated inhibitory receptor PD-1, suggesting that induction of exhaustion may be a therapeutic strategy in autoimmune and inflammatory disease. Using expression of optimal surrogate markers of co-stimulation/exhaustion signatures in independent data sets, we confirm an association with good clinical outcome or response to therapy in infection (hepatitis C virus) and vaccination (yellow fever, malaria, influenza), but poor outcome in autoimmune and inflammatory disease (type 1 diabetes, anti-neutrophil cytoplasmic antibody-associated vasculitis, systemic lupus erythematosus, idiopathic pulmonary fibrosis and dengue haemorrhagic fever). Thus, T-cell exhaustion plays a central role in determining outcome in autoimmune disease and targeted manipulation of this process could lead to new therapeutic opportunities.

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A CD8+ T cell transcriptional profile of exhaustion correlates with beneficial outcome in AID and response to immunotherapies.
“Consistently, a CD8 + Tcell transcriptional profile of exhaustion correlates with beneficial outcome in AID 35,59 and response to immunotherapies. 60”
From Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases (2024) · cites this paper as [59]

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Bense, R. D., Sotiriou, C. P., Piccart, M. J., Haanen, J. B. A. G., van Vugt, M. A. T. M., de Vries, E. G. E., Schröder, C. P., & Fehrmann, R. S. N. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djw192 · Cited by 380 · see citing works
Genome-wide CRISPR screens of T cell exhaustion identify chromatin remodeling factors that limit T cell persistence
Belk, J. A., Yao, W., Ly, N., Freitas, K. A., Chen, Y.-T., Shi, Q., Valencia, A. M., Shifrut, E., Kale, N., Yost, K. E., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.06.001 · Cited by 382 · see citing works
“, 2006), T cell exhaustion is now appreciated to occur in diverse disease settings, including cancer and autoimmune disease (McKinney et al., 2015; McLane et al., 2019).”
Background
T Cells in Fibrosis and Fibrotic Diseases
Zhang, M., & Zhang, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01142 · Cited by 333 · see citing works
“T cells can regulate the pulmonary fibrosis outcome through cAMP-regulated chloride channels (11), Fas-Fas ligand (FasL) interactions (12), or T cell exhaustion (13).”
Background
Epigenetic regulation of T cell exhaustion
Belk, J. A., Dániel, B., & Satpathy, A. T. (2022) · Nature Immunology · doi:10.1038/s41590-022-01224-z · Cited by 334 · see citing works
Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells
Bengsch, B., Ohtani, T., Khan, O., Setty, M. N., Manne, S., O’Brien, S., Gherardini, P. F., Herati, R. S., Huang, A. C. C., Chang, K., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.04.026 · Cited by 319 · see citing works
“Tex cells have also been implicated in autoimmune diseases where transcriptional signatures of Tex cells are enriched in patients with less severe disease (McKinney et al., 2015).”
Background
DNA Methylation and Transcription Patterns in Intestinal Epithelial Cells From Pediatric Patients With Inflammatory Bowel Diseases Differentiate Disease Subtypes and Associate With Outcome
Howell, K. J., Kraiczy, J., Nayak, K., Gasparetto, M., Ross, A., Lee, C., Mak, T. N., Koo, B., Kumar, N., Lawley, T. D., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.10.007 · Cited by 315 · see citing works
“We decided to utilize WGCNA, which has been successfully applied to both RNAseq and DNAm datasets, allowing identification and correlation of individual gene modules with clinical parameters.(40) Results are highly encouraging because we discovered a number of gene expression modules that correlated strongly with the…”
Method
A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial
Noor, N. M., Lee, J. C., Bond, S. J., Dowling, F., Brezina, B., Patel, K., Ahmad, T., Banim, P. J. R., Berrill, J., Cooney, R. M., et al. (2024) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(24)00034-7 · Cited by 315 · see citing works
“27,28 Care had been taken during biomarker develop ment to prevent over-fitting and independently validate associations with clinical outcome in two real-world cohorts.”
ResultSelf-citation
Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease
Lee, J. C., Biasci, D., Roberts, R., Gearry, R. B., Mansfield, J. C., Ahmad, T., Prescott, N. J., Satsangi, J., Wilson, D. C., Jostins, L., et al. (2017) · Nature Genetics · doi:10.1038/ng.3755 · Cited by 304 · see citing works
Self-citation
Rethinking peripheral T cell tolerance: checkpoints across a T cell’s journey
ElTanbouly, M. A., & Noelle, R. J. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-00454-2 · Cited by 267 · see citing works
Myasthenia gravis: An emerging toxicity of immune checkpoint inhibitors
Makarious, D., Horwood, K., & Coward, J. I. G. (2017) · European Journal of Cancer · doi:10.1016/j.ejca.2017.05.041 · Cited by 263 · see citing works
“With respect to PD-1, its overexpression is associated with favourable outcomes in autoimmune diseases as it potentiates CD8 T-cell exhaustion; hence, it is feasible that PD-1 inhibition could result in the exacerbation of symptoms in patients with pre-existing MG [31,32].”
Background
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
Ventham, N. T., Kennedy, N. A., Adams, A. T., Kalla, R., Heath, S. C., O'Leary, K. E., Drummond, H., Lauc, G., Campbell, H., McGovern, D. P. B., et al. (2016) · Nature Communications · doi:10.1038/ncomms13507 · Cited by 257 · see citing works
Single-cell atlas of colonic CD8+ T cells in ulcerative colitis
Corridoni, D., Antanaviciute, A., Gupta, T., Fawkner-Corbett, D., Aulicino, A., Jagielowicz, M., Parikh, K., Repapi, E., Taylor, S. L., Ishikawa, D., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1003-4 · Cited by 252 · see citing works
Not-so-opposite ends of the spectrum: CD8+ T cell dysfunction across chronic infection, cancer and autoimmunity
Collier, J. L., Weiss, S. A., Pauken, K. E., Sen, D. R., & Sharpe, A. H. (2021) · Nature Immunology · doi:10.1038/s41590-021-00949-7 · Cited by 237 · see citing works
Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes
Long, S. A., Thorpe, J., DeBerg, H. A., Gersuk, V., Eddy, J. A., Harris, K. M., Ehlers, M., Herold, K. C., Nepom, G. T., & Linsley, P. S. (2016) · Science Immunology · doi:10.1126/sciimmunol.aai7793 · Cited by 250 · see citing works
LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation
Joller, N., Anderson, A. C., & Kuchroo, V. K. (2024) · Immunity · doi:10.1016/j.immuni.2024.01.010 · Cited by 287 · see citing works
Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis
Zhang, H., Watanabe, R., Berry, G. J., Vaglio, A., Liao, Y. J., Warrington, K. J., Goronzy, J. J., & Weyand, C. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1616848114 · Cited by 246 · see citing works
“signatures was predictive of clinical outcomes in infectious versus autoimmune diseases (54).”
Background
Suppression by TFR cells leads to durable and selective inhibition of B cell effector function
Sage, P. T., Ron‐Harel, N., Juneja, V. R., Sen, D. R., Maleri, S., Sungnak, W., Kuchroo, V. K., Haining, W. N., Chevrier, N., Haigis, M. C., et al. (2016) · Nature Immunology · doi:10.1038/ni.3578 · Cited by 236 · see citing works
The Interplay Between Neutrophils and CD8+ T Cells Improves Survival in Human Colorectal Cancer
Governa, V., Trella, E., Mele, V., Tornillo, L., Amicarella, F., Cremonesi, E., Muraro, M. G., Xu, H., Droeser, R. A., Däster, S., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2047 · Cited by 237 · see citing works
“To further characterize neutrophil-mediated costimulation of CD8þ T cells, we evaluated phenotypic profiles of lymphocytes activated by optimal anti-CD3 concentrations and CD28 in the presence or absence of granulocytes for 5 days, thus, beyond time points usually considered for detection of maximal proliferation (31).”
BackgroundMethodResult
Rheumatic immune-related adverse events from cancer immunotherapy
Calabrese, L. H., Calabrese, C. M., & Cappelli, L. C. (2018) · Nature Reviews Rheumatology · doi:10.1038/s41584-018-0074-9 · Cited by 233 · see citing works
T cells in Systemic Lupus Erythematosus
Suárez‐Fueyo, A., Bradley, S. J., & Tsokos, G. C. (2016) · Current Opinion in Immunology · doi:10.1016/j.coi.2016.09.001 · Cited by 230 · see citing works
“Induction of exhaustion has been proposed as therapy for autoimmune disease, as an exhaustion transcriptome profile marks patients with better clinical outcomes [10].”
The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity
Schnell, A., Bod, L., Madi, A., & Kuchroo, V. K. (2020) · Cell Research · doi:10.1038/s41422-020-0277-x · Cited by 223 · see citing works
“Additionally, a transcriptional signature of T-cell exhaustion is associated with a favorable clinical outcome in multiple human autoimmune diseases.(31) Based on these data, promoting T-cell exhaustion could be beneficial in autoimmunity, and provides a novel therapeutic approach for inhibiting autoimmunity(31,118) (…”
Background
T cell Allorecognition Pathways in Solid Organ Transplantation
Siu, J. H. Y., Surendrakumar, V., Richards, J. A., & Pettigrew, G. J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02548 · Cited by 223 · see citing works
“It has garnered much attention recently, because it is perhaps not the propensity to trigger self-reactive responses, but the ability, or otherwise, to counter their progression through development of an exhaustive state that may ultimately determine outcomes for autoimmune disease (71, 78).”
Background
Critical Role of CD2 Co-stimulation in Adaptive Natural Killer Cell Responses Revealed in NKG2C-Deficient Humans
Liu, L. L., Landskron, J., Ask, E. H., Enqvist, M., Sohlberg, E., Traherne, J. A., Hammer, Q., Goodridge, J. P., Larsson, S., Jayaraman, J., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.005 · Cited by 222 · see citing works
“It will be of interest to explore whether CD2 costimulation of CD16-driven responses influence the functional reprogramming of the cell during expansion in a fashion similar to that noted in the context of T cell exhaustion in autoimmunity and infection (McKinney et al., 2015).”
Result
The immunology of type 1 diabetes
Herold, K. C., Delong, T., Perdigoto, A. L., Biru, N., Brusko, T. M., & Walker, L. S. K. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-023-00985-4 · Cited by 222 · see citing works
“…cells from treated patients, extend the observational studies that slow rates of sponta-neous disease in at-risk individuals correlate with T cell exhaustion signatures identified in treated patients by expression of an EOMES signature and the expression of TIGIT and KLRG1 on CD8 + T cells 206 .”
Hepatitis B virus–specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation
Rivino, L., Bert, N. L., Gill, U. S., Kunasegaran, K., Cheng, Y., Tan, D., Becht, É., Hansi, N. K., Foster, G. R., Su, T., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci92812 · Cited by 208 · see citing works
“Furthermore, it was recently reported that a transcriptional T cell signature that is linked to CD8+ T cell exhaustion and CD4+ T cell costimulation can predict the outcome of chronic viral infection (12).”
Background
Combined anti‐PD‐1 and anti‐CTLA‐4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action
Willsmore, Z. N., Coumbe, B. G. T., Crescioli, S., Reci, S., Gupta, A., Harris, R. J. C., Chenoweth, A. M., Chauhan, J., Bax, H. J., McCraw, A. J., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202048747 · Cited by 208 · see citing works
C1q restrains autoimmunity and viral infection by regulating CD8 <sup>+</sup> T cell metabolism
Ling, G. S., Crawford, G., Buang, N., Bartok, I., Tian, K., Thielens, N. M., Bally, I., Harker, J. A., Ashton-Rickardt, P. G., Rutschmann, S., et al. (2018) · Science · doi:10.1126/science.aao4555 · Cited by 199 · see citing works
T cell exhaustion: from pathophysiological basics to tumor immunotherapy
Catakovic, K., Klieser, E., Neureiter, D., & Geisberger, R. (2017) · Cell Communication and Signaling · doi:10.1186/s12964-016-0160-z · Cited by 202 · see citing works
“In line with that, presence of exhausted T cells in patients with autoimmune diseases correlates with favorable prognosis [18].”
Background
Validation of a 52-gene risk profile for outcome prediction in patients with idiopathic pulmonary fibrosis: an international, multicentre, cohort study
Herazo-Maya, J. D., Sun, J., Molyneaux, P. L., Li, Q., Villalba, J. A., Tzouvelekis, A., Lynn, H., Juan-Guardela, B. M., Risquez, C., Osorio, J. C., et al. (2017) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(17)30349-1 · Cited by 175 · see citing works
A Dual Immunotherapy Nanoparticle Improves T‐Cell Activation and Cancer Immunotherapy
Mi, Y., Smith, C. C., Yang, F., Qi, Y., Roche, K. C., Serody, J. S., Vincent, B. G., & Wang, A. Z. (2018) · Advanced Materials · doi:10.1002/adma.201706098 · Cited by 198 · see citing works
Identification of Pathogenic Immune Cell Subsets Associated With Checkpoint Inhibitor–Induced Myocarditis
Zhu, H., Galdos, F. X., Lee, D., Waliany, S., Huang, Y. V., Ryan, J., Dang, K., Neal, J. W., Wakelee, H. A., Reddy, S. A., et al. (2022) · Circulation · doi:10.1161/circulationaha.121.056730 · Cited by 192 · see citing works
A blood-based prognostic biomarker in IBD
Biasci, D., Lee, J. C., Noor, N. M., Pombal, D., Hou, M., Lewis, N. R., Ahmad, T., Hart, A. L., Parkes, M., McKinney, E. F., et al. (2019) · Gut · doi:10.1136/gutjnl-2019-318343 · Cited by 190 · see citing works
Self-citation
Human leukocyte antigen variation is associated with adverse events of checkpoint inhibitors
Hasan Ali, O., Berner, F., Bomze, D., Fässler, M., Diem, S., Cozzio, A., Jörger, M., Früh, M., Driessen, C., Lenz, T. L., et al. (2019) · European Journal of Cancer · doi:10.1016/j.ejca.2018.11.009 · Cited by 187 · see citing works
“%) patients were treated with antiePD-1 (nivolumab or pembrolizumab) or anti-PD-L1 (atezolizumab) treatment alone.”
Influential
The advent of immune stimulating CAFs in cancer
Tsoumakidou, M. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00549-7 · Cited by 188 · see citing works
Autoreactive CD8+ T cell exhaustion distinguishes subjects with slow type 1 diabetes progression
Wiedeman, A. E., Muir, V. S., Rosasco, M. G., DeBerg, H. A., Presnell, S., Haas, B., Dufort, M. J., Speake, C., Greenbaum, C. J., Serti, E., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci126595 · Cited by 168 · see citing works
“By contrast, increased CD8+ T cell exhaustion is associated with a beneficial response to therapy in recent-onset T1D (20, 50) as well as slower disease progression or a better prognosis in Crohn’s disease, SLE, and vasculitis (51, 52).”
Background
Translating Immunology into Therapeutic Concepts for Inflammatory Bowel Disease
Uhlig, H. H., & Powrie, F. M. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053055 · Cited by 170 · see citing works
Immunology of COVID‐19: Mechanisms, clinical outcome, diagnostics, and perspectives—A report of the European Academy of Allergy and Clinical Immunology (EAACI)
Sokołowska, M., Łukasik, Z. M., Agache, I. O., Akdiş, C. A., Akdiş, D., Akdiş, M., Barcik, W., Brough, H. A., Eiwegger, T., Eljaszewicz, A., et al. (2020) · Allergy · doi:10.1111/all.14462 · Cited by 169 · see citing works
Functional Anti-TIGIT Antibodies Regulate Development of Autoimmunity and Antitumor Immunity
Dixon, K. O., Schorer, M., Nevin, J. T., Etminan, Y., Amoozgar, Z., Kondo, T., Kurtuluş, S., Kassam, N., Sobel, R. A., Fukumura, D., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1700407 · Cited by 164 · see citing works
“In this context, the role that coinhibitory molecules may play in regulating progression in autoimmune diseases in humans has been indicated in a large cohort of patients suffering with multiple autoimmune diseases (17).”
Background
The CD38/NAD/SIRTUIN1/EZH2 Axis Mitigates Cytotoxic CD8 T Cell Function and Identifies Patients with SLE Prone to Infections
Katsuyama, E., Suárez‐Fueyo, A., Bradley, S. J., Mizui, M., Marín, A. V., Mulki, L., Krishfield, S., Malavasi, F., Yoon, J. H., Sui, S. J. H., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2019.12.014 · Cited by 162 · see citing works
“It should be noted that blockade of PD1/PDL1 in cancer patients with SLE may cause de novo appearance of systemic autoimmunity (Naidoo et al., 2016), and T cell exhaustion may favor autoimmunity albeit worsen viral infections (McKinney et al., 2015).”
IFNγ-mediated repression of system xc− drives vulnerability to induced ferroptosis in hepatocellular carcinoma cells
Kong, R., Wang, N., Han, W., Bao, W., & Lu, J. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ma1220-815rrr · Cited by 162 · see citing works
Kidney-infiltrating T cells in murine lupus nephritis are metabolically and functionally exhausted
Tilstra, J. S., Avery, L., Menk, A. V., Gordon, R. A., Smita, S., Kane, L. P., Chikina, M., Delgoffe, G. M., & Shlomchik, M. J. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120859 · Cited by 149 · see citing works
“While, to our knowledge, exhaustion of T cells within target organs has not been linked to autoimmunity, a recent landmark study correlated the presence of exhausted CD8+ T cells in the peripheral blood with prolonged flare-free survival in lupus and antineutrophil cytoplasmic antibody (ANCA) vasculitis (65).”
Elevated Exhaustion Levels of NK and CD8+ T Cells as Indicators for Progression and Prognosis of COVID-19 Disease
Li, M., Guo, W., Dong, Y., Wang, X., Dai, D., Liu, X., Wu, Y., Li, M., Zhang, W., Zhou, H., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.580237 · Cited by 157 · see citing works
“Programmed death-1 (PD-1) and CD244 are immunoregulatory receptors found onmany immune cell types, including NK cells and T cells, and that represent potential therapeutic targets (21, 22).”
Background
Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score
Carbone, M., Nardi, A., Flack, S., Carpino, G., Varvaropoulou, N., Gavrila, C., Spicer, A., Badrock, J., Bernuzzi, F., Cardinale, V., et al. (2018) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(18)30163-8 · Cited by 155 · see citing works
Resident memory CD8+ T cells in regional lymph nodes mediate immunity to metastatic melanoma
Molodtsov, A. K., Khatwani, N., Vella, J. L., Lewis, K. A., Zhao, Y., Han, J., Sullivan, D. E., Searles, T. G., Preiss, N. K., Shabaneh, T. B., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.08.019 · Cited by 155 · see citing works
Exhaustion of CAR T cells: potential causes and solutions
Kouro, T., Himuro, H., & Sasada, T. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03442-3 · Cited by 151 · see citing works
“While it would be indispensable to stop immune responses at certain stages to prevent adverse effects such as autoimmune diseases [17], it also prevents the effects of cancer immunotherapy; tumor infiltrating T cells frequently become exhausted by excessive antigen stimulation and/or inhibitory TME [18].”
Background
The pathogenesis of systemic lupus erythematosus: Harnessing big data to understand the molecular basis of lupus
Catalina, M. D., Owen, K. A., Labonte, A. C., Grammer, A. C., & Lipsky, P. E. (2019) · Journal of Autoimmunity · doi:10.1016/j.jaut.2019.102359 · Cited by 145 · see citing works
SLE: Another Autoimmune Disorder Influenced by Microbes and Diet?
Mu, Q., Zhang, H., & Luo, X. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00608 · Cited by 141 · see citing works
“T cell exhaustion during chronic infection may explain the ability of these pathogens to down-regulate inflammation and ameliorate SLE (49, 50).”
Background
Cell type-specific gene expression patterns associated with posttraumatic stress disorder in World Trade Center responders
Kuan, P. F., Yang, X., Clouston, S., Ren, X., Kotov, R., Waszczuk, M. A., Singh, P. K., Glenn, S. T., Gomez, E. C., Wang, J., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-018-0355-8 · Cited by 137 · see citing works
Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus
Accapezzato, D., Caccavale, R., Paroli, M. P., Gioia, C., Nguyen, B. L., Spadea, L., & Paroli, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076578 · Cited by 146 · see citing works
A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals
Demetriou, P., Abu‐Shah, E., Valvo, S., McCuaig, S., Mayya, V., Kvalvaag, A. S., Starkey, T., Korobchevskaya, K., Lee, L. Y. W., Friedrich, M., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0770-x · Cited by 131 · see citing works
The Multifaceted Role of Tissue-Resident Memory T Cells.
Christo, S., Park, S. L., Mueller, S. N., & Mackay, L. K. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101320-020220 · Cited by 120 · see citing works
Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story
Quaglia, M., Merlotti, G., Andrea, M. D., Borgogna, C., & Cantaluppi, V. (2021) · Viruses · doi:10.3390/v13020277 · Cited by 127 · see citing works
PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation
Petrelli, A., Mijnheer, G., van Konijnenburg, D. P. H., van der Wal, M. M., Giovannone, B., Mocholi, E., Vazirpanah, N., Broen, J. C., Hijnen, D., Oldenburg, B., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96107 · Cited by 126 · see citing works
SARS-CoV-2 triggering autoimmune diseases
Mobasheri, L., Nasirpour, M. H., Masoumi, E., Azarnaminy, A. F., Jafari, M., & Esmaeili, S. (2022) · Cytokine · doi:10.1016/j.cyto.2022.155873 · Cited by 125 · see citing works
High-dimensional single-cell analysis reveals the immune signature of narcolepsy
Hartmann, F. J., Bernard‐Valnet, R., Queriault, C., Mrdjen, D., Weber, L. M., Galli, E., Krieg, C., Robinson, M. D., Nguyen, X., Dauvilliers, Y. A., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20160897 · Cited by 120 · see citing works
“Precedent for broad T cell alterations in organ-specific autoimmune diseases has been reported, although the exact mechanisms involved still escape current understanding (McKinney et al., 2015).”
Background
Anti-PD-1/PD-L1 therapy for infectious diseases: learning from the cancer paradigm
Rao, M., Valentini, D., Dodoo, E., Zumla, A. I., & Maeurer, M. J. (2017) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2017.01.028 · Cited by 122 · see citing works
“Biologically, PD-1 expression may play a beneficial role in ameliorating and curbing the development of autoimmune disease although this is not true for cancer and infections.(12) PD-1 expression on T-cells identifies immune cells that specifically recognize and react to transformed as well as to pathogen-derived anti…”
Background
New Insights on CD8+ T Cells in Inflammatory Bowel Disease and Therapeutic Approaches
Casalegno‐Garduño, R., & Däbritz, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.738762 · Cited by 123 · see citing works
MultiPLIER: A Transfer Learning Framework for Transcriptomics Reveals Systemic Features of Rare Disease
Taroni, J., Grayson, P. C., Hu, Q., Eddy, S. F., Kretzler, M., Merkel, P. A., & Greene, C. S. (2019) · Cell Systems · doi:10.1016/j.cels.2019.04.003 · Cited by 120 · see citing works
“…brushing microarray dataset (NARES dataset) that included patients with granulomatosis with polyangiitis (GPA), sarcoidosis, and healthy controls (Grayson et al., 2015) and a microarray dataset of isolated immune cell types from different autoimmune conditions (E-MTAB-2452; McKinney et al., 2015).”
Background
Immune aging in diabetes and its implications in wound healing
Moura, J., Madureira, P., Leal, E. C., Fonseca, A. C., & Carvalho, E. (2019) · Clinical Immunology · doi:10.1016/j.clim.2019.02.002 · Cited by 116 · see citing works
Human epigenetic and transcriptional T cell differentiation atlas for identifying functional T cell-specific enhancers
Giles, J. R., Manne, S., Freilich, E., Oldridge, D. A., Baxter, A. E., George, S. M., Chen, Z., Huang, H., Chilukuri, L., Carberry, M., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.02.004 · Cited by 114 · see citing works
Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus
Buang, N., Tapeng, L., Gray, V., Sardini, A., Whilding, C., Lightstone, L., Cairns, T. D., Pickering, M. C., Behmoaras, J., Ling, G. S., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22312-y · Cited by 118 · see citing works
Current Status of Companion and Complementary Diagnostics: Strategic Considerations for Development and Launch
Scheerens, H., Malong, A., Bassett, K., Boyd, Z. S., Gupta, V., Harris, J. M., Mesick, C. P., Simnett, S., Stevens, H., Gilbert, H., et al. (2017) · Clinical and Translational Science · doi:10.1111/cts.12455 · Cited by 118 · see citing works
Reduced Nasal Viral Load and IFN Responses in Infants with Respiratory Syncytial Virus Bronchiolitis and Respiratory Failure
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PD-1 immunobiology in systemic lupus erythematosus
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Authors: McKinney, E. F., Lee, J. C., Jayne, D. R. W., Lyons, P. A., & Smith, K. G. C.
Affiliations: University of Cambridge (GB)
Corresponding author: McKinney, Eoin F.
Smith, Kenneth G. C.
ORCID: McKinney, Eoin F.
Lee, James C.
Jayne, David R. W.
Lyons, Paul A.
Smith, Kenneth G. C.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2015-06-29
Volume: 523
Issue: 7562
Pages: 612-616
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature14468
PMC: PMC4623162
OpenAlex: W2103056503
Cited by: 685
References: 56
Citations by year: 2026: 45 · 2025: 54 · 2024: 82 · 2023: 45 · 2022: 81 · 2021: 65 · 2020: 73 · 2019: 74 · 2018: 65 · 2017: 48 · 2016: 40 · 2015: 10 · 2014: 1 · 2013: 1
FWCI: 26.79
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Apollo (University of Cambridge) (submittedVersion)
Apollo
Funders: Wellcome Trust (083650/Z/07/Z, 104064, 104064/Z/14/Z, 100140, 079895/Z/06/Z, 083650, 079895, 100140/Z/12/Z, 094227, 094227/Z/10/Z, 079895/Z/06/B)
Medical Research Council (MR/L019027/1)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords: T cell exhaustion, CD8+ T cells, PD-1, chronic viral infection, autoimmune disease, inflammatory diseases, prognosis, hepatitis C virus, vaccine response, type 1 diabetes, systemic lupus erythematosus, antineutrophil cytoplasmic antibody-associated vasculitis, idiopathic pulmonary fibrosis, dengue hemorrhagic fever, gene expression signatures, autoreactivity
MeSH terms: Animals, Autoimmune Diseases, Humans, Infections, Inflammation, Lupus Erythematosus, Systemic, Phenotype, Receptors, Antigen, T-Cell, Inflammatory Bowel Diseases, CD4-Positive T-Lymphocytes, Autoimmunity, CD8-Positive T-Lymphocytes, CD2 Antigens, Receptors, Interleukin-7, Mice, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Transcriptome, Programmed Cell Death 1 Receptor

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T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection

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