TCR stimulation protects CD8(+) T cells from CD95 mediated apoptosis

Activation of T cells through the T-cell receptor (TCR) induces the express ion of Fas Ligand (CD95L). In turn, CD95L binds to the Fas receptor (CD95) and rapidly induces apoptosis in cycling cells. This interaction is involve d in the elimination of reactive lymphocytes during an immune response. How ever, TCR activation cannot always trigger apoptosis because an effective i mmune response would then be compromised. Here we show that a short (2 to 3 h) activation of T cells through the TCR simultaneously induces an increas e in CD95L mRNA and a dramatic decrease in caspase-8 mRNA levels and proteo lytic activity in human CD8(+) T cells. In addition, there is a small reduc tion in CD95 mRNA and CD95 levels on the cell surface. We found that preact ivation of T cells protected them from apoptosis induced by either religati on of the TCR or direct exposure to CD95L. These results suggest a mechanis m by which cycling CD95-sensitive peripheral T cells, become protected from CD95 mediated deletion when actively engaged in the specific recognition o f target cells. Human Immunology 62, 32-38 (2001). (C) American Society for Histocompatibility and Immunogenetics, 2001. Published by Elsevier Science Inc.