Transforming growth factor-beta 1 inhibits murine immediate and delayed type hypersensitivity

Transforming growth factor beta 1 (TGF-beta 1) is a member of a gene superfamily that regulates growth, differentiation, and function of cells including several in vitro immune functions. Our study examined the systemic effect of TGF-beta 1 on murine delayed-type hypersensitivity (DTH), a model of T cell-mediated immunity that may depend on mast cells. Mice were immunized by i.v. injection of SRBC or by topical application of picryl chloride, and the responses were elicited by cutaneous challenge with the appropriate Ag. Systemic administration of TGF-beta 1 at the time of Ag challenge significantly reduced both the early and late phases of DTH. The effect of TGF-beta 1 on the release of serotonin from mouse peritoneal mast cells was examined. Results indicated that in vivo treatment with TGF-beta 1 24 h before mast cell harvest inhibited the in vitro release of serotonin in response to challenge with compound 48/80, or anti-IgE antibody. In contrast, treatment with TGF-beta 1 24 h before Ag challenge did not inhibit DTH indicating that mast cells may not be the direct target for TGF-beta 1 in the DTH models. In vivo treatment with TGF-beta 1 inhibited the IgE-mediated, mast cell-dependent, immediate hypersensitivity skin swelling response when injected at the time of, or 24 h before challenge. This suggests an effect on mast cells and a regulatory role for TGF-beta 1 in IgE-mediated responses.