Low dose TGF-beta attenuates IL-12 responsiveness in murine Th cells

• Published in: The Journal of immunology (1950) 1998-08, Vol.161 (4), p.1664-1670
• Main Authors: Gorham, J D, Güler, M L, Fenoglio, D, Gubler, U, Murphy, K M
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antibodies, Monoclonal - pharmacology; Cell Line; Cells, Cultured; Dose-Response Relationship, Immunologic; Interleukin-12 - metabolism; Interleukin-12 - physiology; Lymph Nodes; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Mice; Mice, Inbred BALB C; Mice, Transgenic; Receptors, Interleukin - biosynthesis; Receptors, Interleukin-12; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Transforming Growth Factor beta - immunology; Transforming Growth Factor beta - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.161.4.1664

Expression of IL-12Rs is one important checkpoint for Th1 development. BALB/c DO11.10 CD4+ T cells stimulated by Ag in neutral conditions lose expression of the IL-12R beta 2 subunit and become unresponsive to IL-12. In contrast, B10.D2 or F1 (BALB/c x B10.D2) DO11.10 CD4+ T cells maintain IL-12R beta 2 expression when stimulated similarly. Here we show that the loss of IL-12 responsiveness by BALB/c T cells involves the action of endogenous TGF-beta. BALB/c T cells stimulated in the presence of anti-TGF-beta specifically maintain IL-12 responsiveness, express IL-12R beta 2 mRNA, and can stimulate nitric oxide production in peritoneal exudate cells. Low concentrations of TGF-beta added exogenously during primary activation of B10.D2 or F1 T cells significantly inhibit their development of IL-12 responsiveness. These effects of anti-TGF-beta are dependent on endogenous IFN-gamma and are inhibited by exogenously added IL-4. Thus, at least one effect of TGF-beta on Th1/Th2 development may be the attenuation of IL-12R beta 2 expression.