| First Author | Cobb D | Year | 2009 |
| Journal | Immunology | Volume | 128 |
| Issue | 4 | Pages | 589-99 |
| PubMed ID | 19824916 | Mgi Jnum | J:162286 |
| Mgi Id | MGI:4818551 | Doi | 10.1111/j.1365-2567.2009.03169.x |
| Citation | Cobb D, et al. (2009) T-bet-dependent regulation of CD8+ T-cell expansion during experimental Trypanosoma cruzi infection. Immunology 128(4):589-99 |
| abstractText | 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 naive 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. |
