To induce proper immune responses, T lymphocytes require two types of stimu
li, anti gen-specific and costimulatory signals. Among costimulatory molecu
les, CD28-engagement promotes the survival and proliferation of both naive
and memory T cells. In addition, it is now believed that Fas may play a rol
e in T cell activation in the human system. It is, however, controversial w
hether Fas can act as a costimulatory signal in the murine system. Thus, we
investigated fundamental differences in the capacity to induce proliferati
on of T cells between Fas and CD28 in mice. Fas-mediated T cell proliferati
on was observed only with a full mitogenic dose of anti-CD3 antibodies, whe
reas CD28 engagement was able to enhance T cell proliferation in the presen
ce of a suboptimal level of anti-CD3 antibody. Furthermore, Fas-engaged T c
ells showed faster response in the upregulation of CD25 and CD69 expression
than CD28-engaged ones. Here, we report that Fas might play a role in matu
re T cell activation in the mouse system through a different mechanism from
that in CD28 costimulation.