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Am J Physiol Gastrointest Liver Physiol 295: G485-G492, 2008. First published July 10, 2008; doi:10.1152/ajpgi.90221.2008
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INFLAMMATION/IMMUNITY/MEDIATORS

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

Michael McPherson,1,* Bo Wei,2,* Olga Turovskaya,3 Daisuke Fujiwara,2 Sarah Brewer,2 and Jonathan Braun1,2

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{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.

CD8-positive T lymphocytes; B lymphocytes; immunoregulation; inflammatory bowel disease; cytolysis


Address for reprint requests and other correspondence: J. Braun, Dept. of Pathology and Laboratory Medicine, UCLA, Mailcode 173216, Los Angeles, CA 90095 (e-mail: jbraun{at}mednet.ucla.edu)




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