Innate CD8αα+ lymphocytes enhance anti-CD40 antibody-mediated colitis in mice

Introduction: Immune responses in the intestines require tight regulation to avoid uncontrolled inflammation. We previously described an innate lymphocyte population in the intestinal epithelium (referred to as innate CD8(+), or iCD8 cells) that can protect against gastrointestinal infections such as those mediated by Citrobacter rodentium. Methods: Here, we have evaluated the potential contribution of these cells to intestinal inflammation by analyzing inflammation development in mice with decreased numbers of iCD8 cells. We also determined the potential of iCD8 cells to secrete granzymes and their potential role during inflammatory processes. Results: We found that iCD8 cells play a pro-inflammatory role in the development of disease in a colitis model induced by anti-CD40 antibodies. We further found that the effects of iCD8 cells correlated with their capacity to secrete granzymes. We also observed that the pro-inflammatory properties of iCD8 cells were controlled by interactions of CD8 homodimers on these cells with the thymus leukemia antigen expressed by intestinal epithelial cells. Conclusions: Our findings suggest that iCD8 cells modulate inflammatory responses in the intestinal epithelium, and that dysregulation of iCD8 cells effector functions may enhance disease. We propose that one of the mechanism by which iCD8 cells enhance inflammation is by the secretion of granzymes, which may promote recruitment of infiltrating cells into the epithelium.