Diverse roles for T-bet in the effector responses required for resistance to infection.

J Immunol 2015 Feb 2;194(3):1131-40. Epub 2015 Jan 2.

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;

The transcription factor T-bet has been most prominently linked to NK and T cell production of IFN-γ, a cytokine required for the control of a diverse array of intracellular pathogens. Indeed, in mice challenged with the parasite Toxoplasma gondii, NK and T cell responses are characterized by marked increases of T-bet expression. Unexpectedly, T-bet(-/-) mice infected with T. gondii develop a strong NK cell IFN-γ response that controls parasite replication at the challenge site, but display high parasite burdens at secondary sites colonized by T. gondii and succumb to infection. The loss of T-bet had a modest effect on T cell production of IFN-γ but did not impact on the generation of parasite-specific T cells. However, the absence of T-bet resulted in lower T cell expression of CD11a, Ly6C, KLRG-1, and CXCR3 and fewer parasite-specific T cells at secondary sites of infection, associated with a defect in parasite control at these sites. Together, these data highlight T-bet-independent pathways to IFN-γ production and reveal a novel role for this transcription factor in coordinating the T cell responses necessary to control this infection in peripheral tissues.

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Source
http://dx.doi.org/10.4049/jimmunol.1401617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297724PMC
February 2015
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