Low dose TGF-beta attenuates IL-12 responsiveness in murine Th cells
| Autor: | J D, Gorham, M L, Güler, D, Fenoglio, U, Gubler, K M, Murphy |
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| Rok vydání: | 1998 |
| Předmět: |
Mice
Inbred BALB C Dose-Response Relationship Immunologic Receptors Interleukin-12 Antibodies Monoclonal Mice Transgenic Receptors Interleukin T-Lymphocytes Helper-Inducer Lymphocyte Activation Interleukin-12 Cell Line Mice Adjuvants Immunologic Transforming Growth Factor beta Animals Lymph Nodes Cells Cultured |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 161(4) |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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