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INFLAMMATION/IMMUNITY/MEDIATORS
1Molecular Biology Institute, 2Department of Pathology and Laboratory Medicine, University of California, Los Angeles; and 3La Jolla Institute for Allergy and Immunology, San Diego, California
Submitted 5 March 2008 ; accepted in final form 7 July 2008
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 immune-mediated colitis. The genetic requirements for B cells and CD8+ T cells to confer protective immunoregulation were assessed by cotransfer with colitogenic G
i2–/– T cells into immune-deficient mice. Disease activity in G
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.
CD8-positive T lymphocytes; B lymphocytes; immunoregulation; inflammatory bowel disease; cytolysis
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