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Cited by 801

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 access
Walunas, T L, Bakker, C Y, Bluestone, J A·1996·The Journal of experimental medicine

Abstract

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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Metadata

Authors
Walunas, T. L., Bakker, C. Y., & Bluestone, J. A.
Venue
The Journal of experimental medicine
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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CoChat. (2026). Citation check: CTLA-4 ligation blocks CD28-dependent T cell activation. https://app.cochat.ai/papers/10.1084/jem.183.6.2541
The paper
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).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.