Work

Mechanism of Transforming Growth Factor β–induced Inhibition of T Helper Type 1 Differentiation

Year: 2002

Type: article

Abstract: 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.

Source: The Journal of Experimental Medicine

DOI: 10.1084/jem.20012076

Authors: Leonid Gorelik, Stephanie Constant, Richard A. Flavell

Institutions: Howard Hughes Medical Institute, Yale University

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Howard Hughes Medical Institute, National Institutes of Health, U.S. Public Health Service, National Institute of Allergy and Infectious Diseases