Mm. Bertagnolli et al., EVIDENCE THAT RAPAMYCIN INHIBITS INTERLEUKIN-INDUCED PROLIFERATION OFACTIVATED T-LYMPHOCYTES, Transplantation, 58(10), 1994, pp. 1091-1096
Interleukin 12 is a heterodimeric cytokine involved in the regulation
of natural killer cell. and T lymphocyte responses. In previous studie
s, we found that IL-12 induces proliferation of T cells only after cos
timulation with lectin, alloantigen, or anti-CD3 antibody. The IL-2-me
diated proliferation of long-term T cell lines generated in this fashi
on is typically insensitive to the immunosuppressive agent, cyclospori
ne but sensitive to rapamycin. In this study, we examined the effect o
f cyclosporine and rapamycin on T cells responsive to IL-12. For long-
term cultured T cell lines stimulated with phytohemagglutinin, alloant
igen, or solid-phase anti-CD3 antibody, rapamycin blocked IL-12-induce
d proliferation to background levels. Culture in cyclosporine produced
minimal inhibition of IL-12-induced T cell proliferation. Freshly iso
lated CD3(+) cells did not proliferate in response to IL-12, nor did c
ulture of these cells in IL-12 lead to upregulation of IL-2 receptor.
These data suggest that the effect of IL-12, an important growth regul
ator for activated T lymphocytes, may involve late cellular activation
events.