Localisation of CD8+T_RM 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 (T_RM cell) phenotype. Intestinal CD8+ T_RM cells remain in the tissue to provide local protection against future infections. The control of T_RM 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+ T_RM 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+ T_RM cells to distinct microenvironments …