Integration of B cells and CD8+ T in the protective regulation of systemic epithelial inflammation

Mechanisms that control abnormal CD4+ T cell-mediated tissue damage are a significant factor in averting and resolving chronic inflammatory epithelial diseases. B cells can promote such immunoregulation, and this is thought to involve interaction with MHC II- or CD1-restricted regulatory T cells. The purpose of this study is to genetically define the interacting cells targeted by protective B cells, and to elucidate their regulatory mechanisms in CD4+ T cell inflammation. Transfer of Gαi2−/− CD3+ T cells into lymphopenic mice causes a dose-dependent multi-organ inflammatory disease including the skin, intestine, and lungs. Disease activity is associated with elevated levels of serum TNF-α and IFN-γ, and an activated IL-17 producing CD4+ T cell population. Mesenteric node B cells from wild type mice suppress disease activity, serum cytokine expression, and levels of CD4+ T cells producing TNF-α IFN-γ, and IL-17. The protective function of B cells requires genetic sufficiency of IL-10, MHC I and TAP1. Regulatory B cells induce the expansion and activation of CD8+ T cells, which is correlated with disease protection. These results demonstrate that CD8+ T cells can ameliorate lymphopenic systemic inflammatory disease, through peptide/MHC I-dependent B cell interaction.