T-bet is Required for Optimal Production of IFN-gamma and Antigen-specific T Cell Activation by Dendritic Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 Jun 13

PMID 12802010

Citations 115

Authors

Geanncarlo Lugo-Villarino

Roberto Maldonado-Lopez

Richard Possemato

Cristina Penaranda

Laurie H Glimcher

Affiliations

Soon will be listed here.

Abstract

IFN-gamma is well known as the signature cytokine of CD4+ T helper 1, CD8+, and natural killer cells, but recent studies demonstrate that antigen-presenting cells, in particular dendritic cells (DCs), are another potent source for this proinflammatory cytokine. T-bet, a transcription factor that controls IFN-gamma expression in CD4+ T cells, was reported recently to be expressed in human monocytes and myeloid DCs. In this study we investigate the role of T-bet in this important cell type. The development, differentiation, and activation of bone marrow and splenic DCs were unimpaired in mice lacking T-bet. However, T-bet was essential for the optimal production of IFN-gamma by both CD8alpha+ and CD8alpha- DCs. T-bet-deficient DCs were significantly impaired in their capacity to secrete IFN-gamma after both stimulation with IL-12 alone or in combination with IL-18. Further, T-bet-/- DCs were impaired in their ability to activate the T helper 1 program of adoptively transferred antigen-specific T cells in vivo. The rapid up-regulation of T-bet by IFN-gamma in DCs coupled with a function for DC-derived IFN-gamma in T cell activation may constitute a positive feedback loop to maximize type 1 immunity.

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