| First Author | Gorelik L | Year | 2002 |
| Journal | J Exp Med | Volume | 195 |
| Issue | 11 | Pages | 1499-505 |
| PubMed ID | 12045248 | Mgi Jnum | J:97553 |
| Mgi Id | MGI:3575714 | Doi | 10.1084/jem.20012076 |
| Citation | Gorelik L, et al. (2002) Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation. J Exp Med 195(11):1499-505 |
| abstractText | Regulation by transforming growth factor (TGF)-beta plays an important role in immune homeostasis. TGF-beta inhibits T cell functions by blocking both proliferation and differentiation. Here we show that TGF-beta blocks Th1 differentiation by inhibiting the expression of T-bet, the apparent masterregulator of T helper (Th)1 differentiation. Restoration of T-bet expression through retroviral transduction of T-bet into developing Th1 cells abrogated the inhibitory effect of TGF-beta. In addition, we show that, contrary to prior suggestions, downregulation of interleukin 12 receptor beta2 chain is not key to the TGF-beta-mediated effect. Furthermore, we show that the direct inhibitory effect of TGF-beta on T cells is responsible, at least in part, for the inability of BALB/c mice to mount a Leishmania-specific Th1 response and to clear Leishmanial infection. |
