| First Author | Smeltz RB | Year | 2005 |
| Journal | Immunology | Volume | 114 |
| Issue | 4 | Pages | 484-92 |
| PubMed ID | 15804285 | Mgi Jnum | J:97437 |
| Mgi Id | MGI:3575454 | Doi | 10.1111/j.1365-2567.2005.02115.x |
| Citation | Smeltz RB, et al. (2005) Transforming growth factor-beta1 enhances the interferon-gamma-dependent, interleukin-12-independent pathway of T helper 1 cell differentiation. Immunology 114(4):484-92 |
| abstractText | Transforming growth factor (TGF)-beta, a pleiotropic cytokine that has multiple effects on immune responses, has been shown to inhibit interleukin (IL)-4/GATA-3 expression as well as T helper 2 (Th2) differentiation. Consistent with these reports, we found that priming T cells from DO11.10 transgenic mice with antigen in the presence of TGF-beta inhibited GATA-3 expression and the development of IL-4-producing T cells. Unexpectedly, the inhibition of Th2 development was accompanied by a substantial increase in the number of interferon-gamma (IFN-gamma)-producing cells. T cells primed with TGF-beta secreted IFN-gamma in response to both T-cell receptor ligation and IL-12/IL-18 stimulation, and expressed high levels of T-bet and low levels of GATA-3. The TGF-beta-mediated enhancement of T helper 1 (Th1) priming was independent of IL-12 and signal transducer and activator of transcription (STAT)-4, but required endogenous IFN-gamma. TGF-beta-mediated enhancement of the IFN-gamma-dependent, IL-12-independent pathway of Th1 priming was mediated primarily by the inhibition of IL-4 produced by memory/activated T cells in the unfractionated CD4+ responder population. Nevertheless, TGF-beta did not inhibit this pathway of Th1 differentiation when purified naive CD4+ T cells were used as responders. These data have important implications for strategies being considered for the use of TGF-beta-producing T cells for the treatment of autoimmune disorders. |
