Hh. Oberg et al., ACTIVATION-INDUCED T-CELL DEATH - RESISTANCE OR SUSCEPTIBILITY CORRELATE WITH CELL-SURFACE FAS LIGAND EXPRESSION AND T-HELPER PHENOTYPE, Cellular immunology, 181(1), 1997, pp. 93-100
Activated T cells undergo apoptosis when the Fas-antigen (Apo-1, CD95)
is ligated by Fas ligand molecules (FasL) or agonistic anti-Fas antib
odies. Restimulation of T lymphocytes via the TCR/CD3 complex induces
activation-induced cell death (AICD). AICD and Fas-induced cell death
are causally related since TCR-induced AICD at least in part depends o
n Fas/FasL interactions. Thus, restimulation of T cells leads to FasL
gene transcription and surface expression. Membrane-bound or secreted
FasL molecules then bind to Fas receptors on the same cell or on a nei
ghbor cell to trigger the death signaling cascade. We have compared Fa
s-mediated apoptosis and AICD in a panel of human T cell clones. While
all clones were killed by anti-Fas mAb, several clones were resistant
to AICD triggered by anti-TCR/CD3 mAb or superantigen. The pattern of
TCR-induced protein tyrosine phosphorylation was comparable in AICD-r
esistant and -susceptible clones, as was the induction of FasL mRNA. H
owever, significant differences were observed at the level of FasL sur
face expression which was induced in AICD-susceptible but not in AICD-
resistant clones. Cytokine profiles of CD3-stimulated clone cells supp
ort the recent observations that AICD sensitivity is restricted to the
Th1 subset. However, AICD-resistance is not only associated with the
classical Th2 phenotype. (C) 1997 Academic Press.