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T‐bet‐dependent regulation of CD8 + T‐cell expansion during experimental Trypanosoma cruzi infection
Author(s) -
Cobb Dustin,
Guo Siqi,
Lara Ana M.,
Manque Patricio,
Buck Gregory,
Smeltz Ronald B.
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03169.x
Subject(s) - cytotoxic t cell , biology , il 2 receptor , t cell , cd8 , microbiology and biotechnology , antigen , cd40 , interleukin 21 , antigen presenting cell , immunology , immune system , in vitro , biochemistry
Summary The transcription factor T‐bet (T‐box, expressed in T cells), promotes type I immunity to pathogens through effects involving T cells and dendritic cells. In CD8 + T cells, many of the functions of T‐bet are redundant with those of eomesodermin (Eomes), a paralogue of T‐bet. We therefore investigated the role of T‐bet in immunity to Trypanosoma cruzi , an intracellular pathogen that causes Chagas disease, and which requires CD8 + T cells for resistance. T‐bet‐deficient mice (tbx21 −/− ) were highly susceptible to T. cruzi infection, marked by severe liver pathology. CD8 + T cells from infected tbx21 −/− mice expressed typical markers of activation, including CD44 and CD25. In striking contrast, there was a 10‐fold reduction in the number of antigen‐specific CD8 + T cells in tbx21 −/− mice. This reduction was not a consequence of increased apoptosis or altered tissue‐specific migration. Further, antigen‐presenting cell (APC) functions in tbx21 −/− mice were normal as we observed comparable levels of B7‐1, B7‐2 and CD40 expression as well as normal antigen‐driven proliferation of wild‐type CD8 + T cells in infected tbx21 −/− mice. However, adoptive transfer of naïve T cells from tbx21 −/− donors into infected Rag‐2‐deficient mice (tbx21 +/+ ) demonstrated a similar quantitative defect in CD8 + T‐cell expansion. These data demonstrate that T‐bet facilitates immunity to T. cruzi by promoting the expansion of T. cruzi ‐specific CD8 + T cells in a T cell‐intrinsic manner. They also serve to further illustrate the multifaceted functions of T‐box proteins in regulating quantitative aspects of T‐cell immunity, in addition to qualitative components such as cytokine production.