The C-class chemokine lymphotactin costimulates the apoptosis of human CD4+ T cells

Clonal expansion of activated T cells is controlled by homeostatic mechanis ms leading to cell death of a large proportion of the cells. The CD3/TcR pa thway induces cell death, mostly when triggered in the absence of costimula tory signal. The unique T cell-specific chemokine of the C class, lymphotac tin (Lptn), has recently been shown to inhibit the production of Th1-type l ymphokines in human CD4(+) T cells. The present study shows the ability of Lptn to costimulate the death of CD4+ T lymphocytes triggered through CD3/T CR. The Lptn-mediated increased cell death exhibited characteristic feature s of apoptosis, as mainly determined by DNA fragmentation and exposure of a n apoptotic-specific mitochondrial antigen. This apoptosis was dependent on Fas/ FasL signaling, was not rescued by addition of interleukin 2, and pro ceeded with a predominant processing of both initiator procaspase-9 and eff ector procaspase-7. These caspase activities were further evidenced by spec ific cleavage of poly(ADP-ribose) polymerase (PARP) and CD3/TCR zeta -chain , but not DNA fragmentation factor (DFF45). This study demonstrates that th e functional repertoire of Lptn in the regulation of human CD4(+) T-lymphoc yte activation includes the ability to costimulate apoptosis. (Blood. 2001; 97:2205-2212) (C) 2001 by The American Society of Hematology.