Evidence that rapamycin inhibits interleukin-12-induced proliferation of activated T lymphocytes

• Published in: Transplantation Vol. 58; no. 10; p. 1091
• Main Authors: Bertagnolli, M M, Yang, L, Herrmann, S H, Kirkman, R L
• Format: Journal Article
• Language: English
• Published: United States 27.11.1994
• Subjects: Antibodies; Binding, Competitive - drug effects; CD3 Complex - immunology; Cells, Cultured; Humans; Interleukin-12 - antagonists & inhibitors; Lymphocyte Activation - drug effects; Polyenes - pharmacology; Receptors, Interleukin-2 - analysis; Sirolimus; T-Lymphocytes - immunology; T-Lymphocytes - ultrastructure; Time Factors
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/00007890-199411000-00006

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.