Colitis immunoregulation by CD8+T cell requires T cell cytotoxicity and B cell peptide antigen presentation
Copyright policy )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 immune-mediated colitis. The genetic requirements for B cells and CD8+T cells to confer protective immunoregulation were assessed by cotransfer with colitogenic Gαi2−/−T cells into immune-deficient mice. Disease activity in Gαi2−/−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.
- University of California, Los Angeles United States
CD4-Positive T-Lymphocytes, Cytotoxicity, Immunologic, Antigen Presentation, B-Lymphocytes, Histocompatibility Antigens Class II, CD8-Positive T-Lymphocytes, Colitis, Adoptive Transfer, Disease Models, Animal, B7-1 Antigen, Animals, Cytokines, ATP-Binding Cassette Transporters, Female, B7-2 Antigen, Intestine, Large, ATP Binding Cassette Transporter, Subfamily B, Member 2, Antigens, CD40 Antigens, GTP-Binding Protein alpha Subunit, Gi2
CD4-Positive T-Lymphocytes, Cytotoxicity, Immunologic, Antigen Presentation, B-Lymphocytes, Histocompatibility Antigens Class II, CD8-Positive T-Lymphocytes, Colitis, Adoptive Transfer, Disease Models, Animal, B7-1 Antigen, Animals, Cytokines, ATP-Binding Cassette Transporters, Female, B7-2 Antigen, Intestine, Large, ATP Binding Cassette Transporter, Subfamily B, Member 2, Antigens, CD40 Antigens, GTP-Binding Protein alpha Subunit, Gi2
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