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, iCD8 alpha cells, characterized by expression of CD8 alpha homodimers. iCD8 alpha cells exhibit innate functional characteristics such as the capacity to engulf and kill bacteria. Development of iCD8 alpha cells depends on expression of interleukin-2 receptor gamma chain (IL-2R gamma c), 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 iCD8 alpha 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 iCD8 alpha cells in immune responses associated with the intestinal epithelium.