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CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells.
Open accessAbstract
While interactions between CD28 and members of the B7 family costimulate and enhance T cell responses, recent evidence indicates that the CD28 homologue CTLA-4 plays a downregulatory role. The mechanism by which this occurs is not clear, but it has been suggested that CTLA-4 terminates ongoing responses of activated T cells, perhaps by induction of apoptosis. Here we demonstrate that CTLA-4 engagement by antibody cross-linking or binding to B7 inhibits proliferation and accumulation of the primary T cell growth factor, IL-2, by cells stimulated with anti-CD3 and anti-CD28. This inhibition is not a result of enhanced cell death. Rather it appears to result from restriction of transition from the G1 to the S phase of the cell cycle. Our observation that upregulation of both the IL-2R alpha chain and the CD69 activation antigen are inhibited by CTLA-4 engagement supplies further evidence that CTLA-4 restricts the progression of T cells to an activated state. Together this data demonstrates that CTLA-4 can regulate T cell activation in the absence of induction of apoptotic cell death.
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Metadata
- Authors
- Krummel, M. F., & Allison, J. P.
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1996-06-01
- Volume
- 183
- Issue
- 6
- Pages
- 2533-2540
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2162466652
- Cited by
- 932
- References
- 3
- FWCI
- 17.38
- Type
- journal article
- Language
- en
- Open access
- bronze
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