CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells - PubMed (original) (raw)

CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells

M F Krummel et al. J Exp Med. 1996.

Abstract

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.

PubMed Disclaimer

Similar articles

Cited by

References

    1. J Immunol. 1980 Dec;125(6):2665-72 - PubMed
    1. Immunity. 1995 Jul;3(1):87-98 - PubMed
    1. Immunogenetics. 1981;14(1-2):53-61 - PubMed
    1. Proc Natl Acad Sci U S A. 1985 Feb;82(3):864-8 - PubMed
    1. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4185-9 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources