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

First Author  McPherson M Year  2008
Journal  Am J Physiol Gastrointest Liver Physiol Volume  295
Issue  3 Pages  G485-92
PubMed ID  18617557 Mgi Jnum  J:141865
Mgi Id  MGI:3819910 Doi  10.1152/ajpgi.90221.2008
Citation  McPherson M, et al. (2008) Colitis immunoregulation by CD8+ T cell requires T cell cytotoxicity and B cell peptide antigen presentation. Am J Physiol Gastrointest Liver Physiol 295(3):G485-92
abstractText  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 Galphai2-/- T cells into immune-deficient mice. Disease activity in Galphai2-/- 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.
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