Evidence that rapamycin inhibits interleukin-12-induced proliferation of activated T lymphocytes.
Interleukin 12 is a heterodimeric cytokine involved in the regulation of natural killer cell and T lymphocyte responses. In previous studies, we found that IL-12 induces proliferation of T cells only after co-stimulation with lectin, alloantigen, or anti-CD3 antibody. The IL-2-mediated proliferation of long-term T cell lines generated in this fashion is typically insensitive to the immunosuppressive agent, cyclosporine but sensitive to rapamycin. In this study, we examined the effect of cyclosporine and rapamycin on T cells responsive to IL-12. For long-term cultured T cell lines stimulated with phytohemagglutinin, alloantigen, or solid-phase anti-CD3 antibody, rapamycin blocked IL-12-induced proliferation to background levels. Culture in cyclosporine produced minimal inhibition of IL-12-induced T cell proliferation. Freshly isolated CD3+ cells did not proliferate in response to IL-12, nor did culture 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 regulator for activated T lymphocytes, may involve late cellular activation events.
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
M M
MM
Bertagnolli
L
L
Yang
S H
SH
Herrmann
R L
RL
Kirkman
D000906:Antibodies; D001667:Binding, Competitive / Q000187:drug effects; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D018664:Interleukin-12 / Q000037:antagonists & inhibitors*; D008213:Lymphocyte Activation / Q000187:drug effects*; D011090:Polyenes / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D020123:Sirolimus; D013601:T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D013997:Time Factors
D000906:Antibodies; D017252:CD3 Complex; D011090:Polyenes; D015375:Receptors, Interleukin-2; D018664:Interleukin-12; D020123:Sirolimus