Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 195, Issue 11, Pages 1499-1505Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20012076
Keywords
T cell; differentiation; TGF-beta; T-bet; Leishmania
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Funding
- NIAID NIH HHS [AI 36529, P01 AI036529] Funding Source: Medline
- PHS HHS [AU 39158] Funding Source: Medline
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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 Till response and to clear Leishmanial infection.
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