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Localisation of CD8+TRM cells in infected intestine determines their phenotype and function
▸ Bergsbaken T, Bevan M. Proinflammatory microenvironments within the intestine regulate the differentiation of tissue-resident CD8+ T cells responding to infection. Nat Immunol 2015;16:406–14.
Effector CD8+ T cells produced during bacterial or viral infection undergo an activation phase. This allows entry into a number of peripheral tissues, including the GI tract. CD8+ T cells then acquire a tissue-resident memory T cell (TRM cell) phenotype. Intestinal CD8+ TRM cells remain in the tissue to provide local protection against future infections. The control of TRM cell development, specifically during local infection, is not well defined. In this study, the recruitment of CD8+ T cells to the intestine and the role that distinct microenvironments within the infected intestine can play in regulating cell development was investigated. The authors used Yersinia pseudotuberculosis (Yptb) infection as a model to study the CD8+ T cell response to a pathogen that causes severe intestinal disease. Yptb is a Gram-negative bacterial pathogen that stimulates a robust antigen-specific CD8+ T cell response; however, this has not been characterised. The authors showed that Yptb induced a robust intestinal CD8+ T cell response, resulting in the development of a mixed population of intestinal CD8+ TRM cells. Some of the antigen-specific CD8+ T cells were dependent on transforming growth factor-β receptor (TGF-βR) signalling, expressed CD103, and were evenly distributed throughout the intestinal epithelium and lamina propria. The remaining cells were CD103− and localised near areas of Yptb infection in the lamina propria, where they controlled bacterial replication. The CD103−CD8+ T cells in the lamina propria did not require TGF-βR signalling like the CD103+ cells but were dependent on CXCR3 for recruitment to areas of bacterial infection and inflammation for their differentiation. Overall, the authors’ findings indicate that the localisation of CD8+ TRM cells to distinct microenvironments …
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