Cited by 1,685T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesCancer Immunotherapy and Biomarkers

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CTLA-4 is a second receptor for the B cell activation antigen B7.

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Linsley, P S, Brady, W, Urnes, M, Grosmaire, L S, Damle, N K, Ledbetter, J A·1991·The Journal of experimental medicine

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Abstract

Functional interactions between T and B lymphocytes are necessary for optimal activation of an immune response. Recently, the T lymphocyte receptor CD28 was shown to bind the B7 counter-receptor on activated B lymphocytes, and subsequently to costimulate interleukin 2 production and T cell proliferation. CTLA-4 is a predicted membrane receptor from cytotoxic T cells that is homologous to CD28 and whose gene maps to the same chromosomal band as the gene for CD28. It is not known, however, if CD28 and CTLA-4 also share functional properties. To investigate functional properties of CTLA-4, we have produced a soluble genetic fusion between the extracellular domain of CTLA-4 and an immunoglobulin C gamma chain. Here, we show that the fusion protein encoded by this construct, CTLA4Ig, bound specifically to B7-transfected Chinese hamster ovary cells and to lymphoblastoid cells. CTLA4Ig also immunoprecipitated B7 from cell surface 125I-labeled extracts of these cells. The avidity of 125I-labeled B7Ig fusion protein for immobilized CTLA4Ig was estimated (Kd approximately 12 nM). Finally, we show that CTLA4Ig was a potent inhibitor of in vitro immune responses dependent upon cellular interactions between T and B lymphocytes. These findings provide direct evidence that, like its structural homologue CD28, CTLA-4 is able to bind the B7 counter-receptor on activated B cells. Lymphocyte interactions involving the B7 counter-receptor are functionally important for alloantigen responses in vitro.

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Saiki, R. K., Scharf, S., Faloona, F., Mullis, K. B., Horn, G. T., Erlich, H. A., & Arnheim, N. (1985) · Science · doi:10.1126/science.2999980 · Cited by 8,956
Adhesion receptors of the immune system
Springer, T. A. (1990) · Nature · doi:10.1038/346425a0 · Cited by 6,477
Approaching the asymptote? Evolution and revolution in immunology.Preprint
Janeway, C. (1989) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1989.054.01.003 · Cited by 3,396
The Immunoglobulin Superfamily: Domains For Cell Surface Recognition
Williams, A., & Barclay, A. N. (1988) · Annual Review of Immunology · doi:10.1146/annurev.iy.06.040188.002121 · Cited by 2,270
A cell culture model for T lymphocyte clonal anergy
Schwartz, R. H. (1990) · Science · doi:10.1126/science.2113314 · Cited by 1,857
A Theory of Self-Nonself Discrimination
Bretscher, P., & Cohn, M. (1970) · Science · doi:10.1126/science.169.3950.1042 · Cited by 1,755
A new member of the immunoglobulin superfamily—CTLA-4
Brunet, J., Denizot, F., Luciani, M., Roux-Rouquié, M., Suzan, M., Mattéi, M., & Golstein, P. (1987) · Nature · doi:10.1038/328267a0 · Cited by 1,307
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Linsley, P. S., Brady, W., Grosmaire, L. S., Aruffo, A. A., Damle, N. K., & Ledbetter, J. A. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.173.3.721 · Cited by 1,126
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Lindstein, T., June, C. H., Ledbetter, J. A., Stella, G. C. L., & Thompson, C. B. (1989) · Science · doi:10.1126/science.2540528 · Cited by 866
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Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system.
Aruffo, A. A., & Seed, B. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.23.8573 · Cited by 787

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“Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a member of the CD28-B7 immunoglobulin superfamily and is the key mediator of immune-response attenuation.(23,24) Inhibiting the activity of CTLA-4 with monoclonal antibodies (mAbs) blocks T-cell inhibitory costimulatory molecules, allowing immune cell activation and expans…”
Background
An update on new immunosuppressive drugs undergoing preclinical and clinical trials: Potential applications in organ transplantation
First, M. R. (1997) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(97)90046-9 · Cited by 33
Immunosuppression through biockade of CD28:B7-mediated costimulatory signals
Judge, T. A., Tang, A., & Turka, L. A. (1996) · Immunologic Research · doi:10.1007/bf02918283 · Cited by 33
Selective Modulation of B-Cell Activation Markers CD86 and I-Ak on Murine Draining Lymph Node Cells Following Allergen or Irritant Treatment
Gerberick, G. F., Cruse, L. W., Miller, C. M., & Ridder, G. M. (1999) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1999.8734 · Cited by 33
Disease-modifying therapies in multiple sclerosis: an update on recent and ongoing trials and future strategies
Wiendl, H., & Kieseier, B. C. (2003) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.12.4.689 · Cited by 33
The Differentiated State of Intestinal Lamina Propria CD4+ T Cells Results in Altered Cytokine Production, Activation Threshold, and Costimulatory Requirements
Hurst, S. D., Cooper, C. J., Sitterding, S. M., Choi, J.-H., Jump, R., Levine, A. D., & Barrett, T. A. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.11.5937 · Cited by 33
“CTLA-4Ig binds to B7-1 and B7- 2 and blocks CD28 and CTLA-4 ligation (32).”
BackgroundMethod
Inhibition of thymocyte negative selection by T cell receptor antagonist peptides
Williams, O., Tanaka, Y., Bix, M., Murdjeva, M., Littman, D. R., & Kioussis, D. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260305 · Cited by 33
Harnessing Bacterial Agents to Modulate the Tumor Microenvironment and Enhance Cancer Immunotherapy
Thomas, C. J., Delgado, K., Sawant, K., Roy, J., Gupta, U., Song, C. S., Poojary, R., de Figueiredo, P., & Song, J. J. (2024) · Cancers · doi:10.3390/cancers16223810 · Cited by 32
A novel pancreatic β-cell targeting bispecific-antibody (BsAb) can prevent the development of Type 1 diabetes in NOD mice
Bhattacharya, P., Fan, J.-L., Haddad, C., Essani, A. E., Gopisetty, A., Elshabrawy, H. A., Vasu, C., & Prabhakar, B. S. (2014) · Clinical Immunology · doi:10.1016/j.clim.2014.04.014 · Cited by 32
“CD80 and CD86) ligands than CD28 and thus competes for binding to B7 ligands [20].”
Background
Abatacept Inhibition of T Cell Priming in Mice by Induction of a Unique Transcriptional Profile That Reduces Their Ability to Activate Antigen‐Presenting Cells
Patakas, A., Ji, R., Weir, W., Connolly, S., Benson, R. A., Nadler, S. G., Brewer, J. M., McInnes, I. B., & Garside, P. (2015) · Arthritis & Rheumatology · doi:10.1002/art.39470 · Cited by 36
Inhibition of T-cell activation by the CTLA4-Fc Abatacept is sufficient to ameliorate proteinuric kidney disease
Herrera, M., Söderberg, M. P., Sabirsh, A., Valastro, B., Mölne, J., Santamaría, B., Valverde, Á. M., Guionaud, S., Heasman, S. C., Bigley, A. L., et al. (2016) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00179.2016 · Cited by 32
“The mechanism of action of Abatacept has clearly been demonstrated as a potent 477 inhibitor of T-cell activation (20) and the lack of B7-1 expression in the animal model and 478 human biopsies suggest that the site of action of Abatacept is not the podocyte.”
Background
The molecular basis of immune regulation in autoimmunity
Yang, S., Gao, C., Li, L., Chang, C., Leung, P. S. C., Gershwin, M. E., & Lian, Z. (2018) · Clinical Science · doi:10.1042/cs20171154 · Cited by 34
The Central Role of Inflammation Associated with Checkpoint Inhibitor Treatments
Vâjâitu, C., DRAGHICI, C. C., Solomon, I., Lisievici, C. V., Popa, A. V., Lupu, M., Căruntu, C., Constantin, M. M., & Voiculescu, V. M. (2018) · Journal of Immunology Research · doi:10.1155/2018/4625472 · Cited by 32
Haploinsufficiency of immune checkpoint receptor CTLA4 induces a distinct neuroinflammatory disorder
Schindler, M. K., Pittaluga, S., Enose‐Akahata, Y., Su, H. C., Rao, V. K., Rump, A., Jacobson, S., Cortese, I. C. M., Reich, D. S., & Uzel, G. (2020) · Journal of Clinical Investigation · doi:10.1172/jci135947 · Cited by 32
“org Volume 130 Number 10 October 2020 Introduction Cytotoxic T lymphocyte antigen 4 (CTLA4) is an essential protein in immune homeostasis that is constitutively expressed on regulatory T cells (Tregs) and upregulated on effector T cells upon activation (1, 2).”
Background
Differential Role of CD80 and CD86 Molecules in the Induction and the Effector Phases of Allergic Rhinitis in Mice
Okano, M., Azuma, M., Yoshino, T., Hattori, H., Nakada, M., Satoskar, A. R., HARN, D. A., Nakayama, E., Akagi, T., & Nishizaki, K. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.164.8.2011072 · Cited by 32
Fed-batch cultivation of transgenic rice cells for the production of hCTLA4Ig using concentrated amino acids
Park, C.-I., Lee, S.-J., Kang, S.-H., Jung, H.-S., Kim, D., & Lim, S. (2009) · Process Biochemistry · doi:10.1016/j.procbio.2009.08.004 · Cited by 32
Cytotoxic T-Lymphocyte Antigen-4 and Programmed Death-1 Function as Negative Regulators of Lymphocyte Activation
Carter, L., & Carreno, B. M. (2003) · Immunologic Research · doi:10.1385/ir:28:1:49 · Cited by 32
Successful Gene Therapy via Intraarticular Injection of Adenovirus Vector Containing CTLA4IgG in a Murine Model of Type II Collagen-Induced Arthritis
Ijima, K., Murakami, M., Okamoto, H., Inobe, M., Chikuma, S., Saito, I., Kanegae, Y., Kawaguchi, Y., Kitabatake, A., & Uede, T. (2001) · Human Gene Therapy · doi:10.1089/104303401750214285 · Cited by 32
“CTLA4 binds to its ligands B7-1 and B7-2 with much greater affinity than does CD28 (Freeman et al ., 1991; Linsley et al ., 1991).”
bcl-2 protects against Fas-based but not perforin-based T cell-mediated cytolysis
Lee, R. K., Spielman, J., & Podack, E. R. (1996) · International Immunology · doi:10.1093/intimm/8.7.991 · Cited by 32
B Lymphocytes as Autoantigen‐presenting Cells in the Amplification of Autoimmunitya
ROTH, R., Gee, R. J., & Mamula, M. J. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb52047.x · Cited by 32
Genomic organization and chromosomal location of the human gene encoding the B-lymphocyte activation antigen B7
Selvakumar, A., Mohanraj, B. K., Eddy, R. L., Shows, T. B., White, P. C., & Dupont, B. (1992) · Immunogenetics · doi:10.1007/bf00661094 · Cited by 32
Human endothelial stimulation of allogeneic T cells via a CTLA-4 independent pathway
Page, C., Thompson, C. B., Yacoub, M. H., & Rose, M. L. (1994) · Transplant Immunology · doi:10.1016/0966-3274(94)90013-2 · Cited by 32
New approaches in metastatic melanoma: biological and molecular targeted therapies
Lejeune, F. J., Rimoldi, D., & Speiser, D. E. (2007) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.7.5.701 · Cited by 32
Amplification of tumor immunity by gene transfer of the co-stimulatory 4-1BB ligand: synergy with the CD28 co-stimulatory pathway
Melero, I., Bach, N., Hellström, K. E., Aruffo, A. A., Mittler, R. S., & Chen, L. (1998) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199803)28:03 · Cited by 215
Cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA-4-Ig) suppresses Staphylococcus aureus-induced CD80, CD86, and pro-inflammatory cytokine expression in human B cells
Liu, P.-C., Ssu, C.-T., Tsao, Y.-P., Liou, T., Tsai, C.-Y., Chou, C., Chen, M., & Leu, C.-M. (2020) · Arthritis Research & Therapy · doi:10.1186/s13075-020-2138-x · Cited by 31
“Similar to its membrane form, soluble CTLA-4-Ig acts by competing with CD28 for CD80/CD86 binding and modulates the costimulatory signaling necessary for full T cell activation [16].”
Background
CNS and PNS manifestation in immune checkpoint inhibitors: A systematic review
Khan, E. I., Shrestha, A. K., Elkhooly, M., Wilson, H. E., Ebbert, M., Srivastava, S., Wen, S., Rollins, S., & Sriwastava, S. (2021) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2021.120089 · Cited by 35
Mesenchymal stem cells augment regulatory T cell function via CD80-mediated interactions and promote allograft survival
Mittal, S. K., Cho, W., Elbasiony, E., Guan, Y., Foulsham, W., & Chauhan, S. K. (2022) · American Journal of Transplantation · doi:10.1111/ajt.17001 · Cited by 31
Immunotherapy of experimental autoimmune myasthenia gravis: selective effects of CTLA4Ig and synergistic combination with an IL2-Diphtheria toxin fusion protein
McIntosh, K. R., Linsley, P. S., Bacha, P. A., & Drachman, D. B. (1998) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00071-x · Cited by 31
Self-citation
Blockade of LIGHT/HVEM and B7/CD28 Signaling Facilitates Long-Term Islet Graft Survival With Development of Allospecific Tolerance
Fan, K., Wang, H., Wei, H., Zhou, Q., Kou, G., Hou, S., Qian, W., Dai, J., Li, B., Zhang, Y., et al. (2007) · Transplantation · doi:10.1097/01.tp.0000280545.14489.df · Cited by 31
AILIM/ICOS: Its Expression and Functional Analysis with Monoclonal Antibodies
Sakamoto, S., Tezuka, K., Tsuji, T., Hori, N., & Tamatani, T. (2001) · Hybridoma and Hybridomics · doi:10.1089/15368590152740699 · Cited by 31
Peripheral T‐cell tolerance: the contribution of permissive T‐cell migration into parenchymal tissues of the neonate
Alferink, J., Aigner, S., Reibke, R., Hämmerling, G. J., & Arnold, B. (1999) · Immunological Reviews · doi:10.1111/j.1600-065x.1999.tb01320.x · Cited by 31
Activation of CD4+ T lymphocytes form interleukin 2-deficient mice by costimulatory B7 molecules.
Razi-Wolf, Z., Holländer, G. A., & Reiser, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.7.2903 · Cited by 31
Treatment of murine lupus with PD-LIg
Zhou, H., Xiong, L., Wang, Y., Ding, L., Hu, S., Zhao, M. F., & Zhou, L. (2015) · Clinical Immunology · doi:10.1016/j.clim.2015.10.006 · Cited by 30
Progress of immune checkpoint therapy in the clinic (Review)
Fan, Y., Zhang, C., Jin, S., Gao, Z., Cao, J., Wang, A., Li, D., Wang, Q., Sun, X., & Bai, D. (2018) · Oncology Reports · doi:10.3892/or.2018.6819 · Cited by 30
“CTLA-4 downregulates the T cell response by displacing CD28 costimulation (8).”
Positive Immuno-Modulation Following Radiofrequency Assisted Liver Resection in Hepatocellular Carcinoma
Huang, K., Jayant, K., Lee, P., Yang, P.-C., Hsiao, C., Habib, N., & Sodergren, M. H. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8030385 · Cited by 30
“CTLA-4 is pivotal for the control of the CD4+ T-cell function, and it essentially staged the priming phase of the cell mediated immune response [58,59].”
Background

Authors: Linsley, P. S., Brady, W., Urnes, M., Grosmaire, L. S., Damle, N. K., & Ledbetter, J. A.
Affiliations: Bristol-Myers Squibb (United States) (US)
ORCID: Linsley, P S
Venue: The Journal of experimental medicine
Publisher: Rockefeller University Press
Published: 1991-09-01
Volume: 174
Issue: 3
Pages: 561-569
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.174.3.561
PMC: PMC2118936
OpenAlex: W2087013294
Cited by: 1,685
References: 41
Citations by year: 2026: 14 · 2025: 31 · 2024: 49 · 2023: 37 · 2022: 35 · 2021: 49 · 2020: 51 · 2019: 55 · 2018: 49 · 2017: 49 · 2016: 59 · 2015: 52 · 2014: 39 · 2013: 41 · 2012: 39
FWCI: 27.78
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Experimental Medicine (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Funders: Bristol-Myers Squibb
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: CTLA-4, B7, CD28, T cell costimulation, B cell activation, T cell-B cell interaction, soluble receptor, interleukin-2, alloantigen response, cytotoxic T lymphocytes
MeSH terms: Abatacept, Amino Acid Sequence, Animals, Antigens, Differentiation, Antigens, Surface, B-Lymphocytes, Base Sequence, Cell Line, Ligands, Lymphocyte Cooperation, Lymphocyte Activation, Molecular Sequence Data, Oligonucleotides, Precipitin Tests, Receptors, Immunologic, Recombinant Fusion Proteins, T-Lymphocytes, Antigens, CD, B7-1 Antigen, Immunoconjugates, CTLA-4 Antigen, In Vitro Techniques

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CTLA-4 is a second receptor for the B cell activation antigen B7.

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