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Smad4 Promotes Differentiation of Effector and Circulating Memory CD8 T Cells but Is Dispensable for Tissue-Resident Memory CD8 T Cells.
- Source :
-
Journal of Immunology . 3/1/2015, Vol. 194 Issue 5, p2407-2414. 8p. - Publication Year :
- 2015
-
Abstract
- Tissue-resident memory CD8 T cells are a unique subset of virus-specific CTLs that bolster local immune responses after becoming lodged in previously infected tissues. These cells provide enhanced protection by intercepting returning pathogens before a new infection gets established. In contrast, central memory CD8 T cells circulate in the bloodstream and proliferate in secondary lymphoid organs before replenishing effector and memory CD8 T cell populations in remote parts of the body. Both populations of virus-specific memory CD8 T cells participate in immunity to influenza virus infection; however, the signaling pathways that instruct developing memory CD8 T cells to distribute to specific tissues are poorly defined. We show that TGF-β promotes the development of pulmonary tissue-resident memory T cells via a signaling pathway that does not require the downstream signaling intermediate Sma- and Mad-related protein (Smad)4. In contrast, circulating memory CD8 T cells have no requirement for TGF-β but show signs of arrested development in the absence of Smad4, including aberrant CD103 expression. These signaling pathways alter the distribution of virus-specific CTLs in the lungs but do not prevent robust cytokine responses. Our data show that Smad4 is required for normal differentiation of multiple subsets of virus-specific CD8 T cells. In normal circumstances, Smad4 may be activated via a pathway that bypasses the TGF-β receptor. Improved understanding of these signaling pathways could be used to augment vaccine-induced immunity. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CD8 antigen
*T cells
*CELLULAR immunity
*INFLUENZA viruses
*CYTOKINES
Subjects
Details
- Language :
- English
- ISSN :
- 00221767
- Volume :
- 194
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Journal of Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 110123583
- Full Text :
- https://doi.org/10.4049/jimmunol.1402369