The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
CTLA-4 ligation blocks CD28-dependent T cell activation.
Open accessAbstract
CTLA-4 is a CD28 homologue believed to be a negative regulator of T cell function. However, the mechanism of this downregulatory activity is not well understood. The present study was designed to examine the effect of CTLA-4 ligation on cytokine production, cell survival, and cell cycle progression. The results demonstrate that the primary effect of CTLA-4 ligation is not the induction of apoptosis. Instead, CTLA-4 signaling blocks IL-2 production, IL-2 receptor expression, and cell cycle progression of activated T cells. Moreover, the effect of CTLA-4 signaling was manifested after initial T cell activation. Inhibition of IL-2 receptor expression and cell cycle progression was more pronounced at late (72 h) time points after initial activation. The effects of anti-CTLA-4 mAbs were most apparent in the presence of optimal CD28-mediated costimulation consistent with the finding that CTLA-4 upregulation was CD28-dependent. Finally, the addition of exogenous IL-2 to the cultures restored IL-2 receptor expression and T cell proliferation. These results suggest that CTLA-4 signaling does not regulate cell survival or responsiveness to IL-2, but does inhibit CD28-dependent IL-2 production.
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Cites
Tivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A., & Sharpe, A. H. (1995) · Immunity · doi:10.1016/1074-7613(95)90125-6 · Cited by 2,914
Self-citationLymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis
Watanabe-Fukunaga, R., Brannan, C. I., Copeland, N. G., Jenkins, N. A., & Nagata, S. (1992) · Nature · doi:10.1038/356314a0 · Cited by 2,885
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., Thompson, C. B., Griesser, H., & Mak, T. W. (1995) · Science · doi:10.1126/science.270.5238.985 · Cited by 2,766
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
Krummel, M. F., & Allison, J. P. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.2.459 · Cited by 2,245
CTLA-4 can function as a negative regulator of T cell activation
Walunas, T. L., Lenschow, D. J., Bakker, C. Y., Linsley, P. S., Freeman, G. J., Green, J. M., Thompson, C. B., & Bluestone, J. A. (1994) · Immunity · doi:10.1016/1074-7613(94)90071-x · Cited by 2,222
Self-citationCTLA-4 is a second receptor for the B cell activation antigen B7.
Linsley, P. S., Brady, W., Urnes, M., Grosmaire, L. S., Damle, N. K., & Ledbetter, J. A. (1991) · The Journal of experimental medicine · doi:10.1084/jem.174.3.561 · Cited by 1,685
Identification of a monoclonal antibody specific for a murine T3 polypeptide.
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Self-citationA new member of the immunoglobulin superfamily—CTLA-4
Brunet, J.-F., Denizot, F., Luciani, M.-F., Roux-Dosseto, M., Suzan, M., Mattei, M.-G., & Golstein, P. (1987) · Nature · doi:10.1038/328267a0 · Cited by 1,306
Unkeless, J. C. (1979) · The Journal of experimental medicine · doi:10.1084/jem.150.3.580 · Cited by 1,237
CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-xL
Boise, L. H., Minn, A. J., Noel, P. J., June, C. H., Accavitti, M. A., Lindsten, T., & Thompson, C. B. (1995) · Immunity · doi:10.1016/1074-7613(95)90161-2 · Cited by 1,210
Cited by
Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., et al. (2001) · Nature Immunology · doi:10.1038/85330 · Cited by 2,955
Dong, H., Zhu, G., Tamada, K., & Chen, L. (1999) · Nature Medicine · doi:10.1038/70932 · Cited by 2,496
Phan, G. Q., Yang, J. C., Sherry, R. M., Hwu, P., Topalian, S. L., Schwartzentruber, D. J., Restifo, N. P., Haworth, L. R., Seipp, C. A., Freezer, L. J., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1533209100 · Cited by 1,575
The CD28 Signaling Pathway Regulates Glucose Metabolism
Frauwirth, K. A., Riley, J. L., Harris, M. H., Parry, R. V., Rathmell, J. C., Plas, D. R., Elstrom, R. L., June, C. H., & Thompson, C. B. (2002) · Immunity · doi:10.1016/s1074-7613(02)00323-0 · Cited by 1,475
Metadata
- Authors
- Walunas, T. L., Bakker, C. Y., & Bluestone, J. A.
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1996-06-01
- Volume
- 183
- Issue
- 6
- Pages
- 2541-2550
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2164903177
- Cited by
- 801
- References
- 41
- FWCI
- 17.38
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Walunas, T. L., Bakker, C. Y., & Bluestone, J. A. (1996). CTLA-4 ligation blocks CD28-dependent T cell activation. The Journal of experimental medicine. https://doi.org/10.1084/jem.183.6.2541
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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