CD8αα+ Innate-Type Lymphocytes in the Intestinal Epithelium Mediate Mucosal Immunity

Innate immune responses are critical for mucosal immunity. Here we describe an innate lymphocyte population, iCD8α cells, characterized by expression of CD8α homodimers. iCD8α cells exhibit innate functional characteristics such as the capacity to engulf and kill bacteria. Development of iCD8α cells depends on expression of interleukin-2 receptor γ chain (IL-2Rγc), IL-15, and the major histocompatibility complex (MHC) class Ib protein H2-T3, also known as the thymus leukemia antigen or TL. While lineage tracking experiments indicated that iCD8α cells have a lymphoid origin, their development was independent of the transcriptional suppressor Id2, suggesting that these cells do not belong to the family of innate lymphoid cells. Finally, we identified cells with a similar phenotype in humans, which were profoundly depleted in newborns with necrotizing enterocolitis. These findings suggest a critical role of iCD8α cells in immune responses associated with the intestinal epithelium. [Display omitted] •iCD8α cells are an innate lymphocyte population in the intestinal epithelium•iCD8α cells depend on IL-2Rγc, IL-15, and H2-T3 for development and maintenance•iCD8α cells are involved in early innate immune responses Innate immune cells are critical for mucosal immunity. Olivares-Villagómez and colleagues report a population of CD8αα+ lymphocytes in the intestinal epithelium of mice and humans that possess innate-like features and contribute to mucosal immune responses.