Colitis immunoregulation by CD8+ T cell requires T cell cytotoxicity and B cell peptide antigen presentation

Deficient immunoregulation by CD4(+) T cells is an important susceptibility trait for inflammatory bowel disease, but the role of other regulatory cell types is less understood. This study addresses the role and mechanistic interaction of B cells and CD8(+) T cells in controlling immunemediated colitis. The genetic requirements for B cells and CD8(+) T cells to confer protective immunoregulation were assessed by cotransfer with colitogenic G alpha i2(-/-) T cells into immune- deficient mice. Disease activity in G alpha i2(-/-) T cell recipients was evaluated by CD4(+) T intestinal lymphocyte abundance, cytokine production levels, and large intestine histology. B cells deficient in B7.1/B7.2, CD40, major histocompatibility complex (MHC) II (Abb), or native B cell antigen receptor (MD4) were competent for colitis protection. However, transporter- 1-deficient B cells failed to protect, indicating a requirement for peptide MHC I presentation to CD8(+) T cells. CD8(+) T cells deficient in native T cell receptor repertoire (OT-1) or cytolysis (perforin(-/-)) also were nonprotective. These finding reveal an integrated role for antigen- specific perforin-dependent CD8(+) T cell cytotoxicity in colitis immunoregulatory and its efficient induction by a subset of mesenteric B lymphocytes.