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Down‐regulation of CD28 via Fas (CD95): influence of CD28 on T‐cell apoptosis
Author(s) -
Lucy Walker,
J Mcleod,
George Boulougouris,
Yusuf Patel,
N. D. Hall,
David M. Sansom
Publication year - 1998
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1998.00490.x
Subject(s) - fas receptor , cd28 , apoptosis , microbiology and biotechnology , biology , cancer research , programmed cell death , t cell , immunology , genetics , immune system
Following antigen engagement of the T‐cell receptor (TCR), T‐cell survival is largely dictated by the provision of additional signals, such as those from costimulatory receptors and cytokine receptors. Whilst CD28‐mediated signalling is increasingly associated with survival, ligation of alternative T‐cell antigens, such as Fas (CD95), can trigger apoptosis. The T‐cell response following antigen engagement may therefore be influenced by the relative expression levels of these coreceptors as well as by the availability of their ligands (CD80/86 and Fas‐L). In this study we demonstrate functional interplay between the death receptor Fas and the costimulatory receptor CD28 in human T cells. In Jurkat T cells, we show that Fas signalling leads to rapid and selective CD28 down‐regulation, and that this is associated with a specific decrease in mRNA for CD28, indicating that mechanisms exist which target CD28 at a transcriptional level. Moreover, cells that down‐regulate CD28 also undergo apoptosis. Studies on activated human peripheral blood T cells demonstrate that cells expressing high levels of CD28 are resistant to Fas‐mediated apoptosis whereas cells expressing low levels are more susceptible, implicating CD28 in the provision of anti‐apoptotic signals. Consistent with this hypothesis, direct ligation of CD28 using B7 transfectants concomitant with anti‐Fas challenge protects from apoptosis. Since antigen‐presenting cells may express Fas‐L under certain circumstances, the maintenance of T‐cell CD28 expression may be crucial for the prevention of Fas‐mediated apoptosis during the course of antigen engagement.