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Department of Internal Medicine II, Chiba University School of Medicine, Chiba, Japan
Memory T cells respond in several functionally different ways from
naive T cells and thus function as efficient effector cells. In this
study we showed that primed T cells were more resistant to Fas-mediated
activation-induced cell death (AICD) than naive T cells using
OVA-specific TCR transgenic DO10 mice and Fas-deficient DO10
lpr/lpr mice. We found that apoptosis was efficiently
induced in activated naive T cells at 48 and 72 h after Ag
restimulation (OVA peptide; 0.3 and 3 µM), whereas apoptosis was not
significantly increased in activated primed T cells at 24–72 h after
Ag restimulation. We further showed that the resistance to AICD in
primed T cells was due to the decreased sensitivity to apoptosis
induced by Fas-mediated signals, but TCR-mediated signaling equally
activated both naive and primed T cells to induce Fas and Fas ligand
expressions. Furthermore, we demonstrated that primed T cells expressed
higher levels of Fas-associated death domain-like IL-1
-converting
enzyme inhibitory protein (FLIP), an inhibitor of Fas-mediated
apoptosis, at 24–48 h after Ag restimulation than naive T cells. In
addition, Bcl-2 expression was equally observed between activated naive
and primed T cells after Ag restimulation. Thus, these results indicate
that naive T cells are sensitive to Fas-mediated AICD and are easily
deleted by Ag restimulation, while primed/memory T cells express higher
levels of FLIP after Ag restimulation, are resistant to Fas-mediated
AICD, and thus function as efficient effector cells for a longer
period.
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