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 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.
McPherson
Michael
M
Molecular Biology Institute, Department of Pathology and Laboratory Medicine, UCLA, Mailcode 173216, Los Angeles, CA 90095, USA.
Wei
Bo
B
Turovskaya
Olga
O
Fujiwara
Daisuke
D
Brewer
Sarah
S
Braun
Jonathan
J
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000235:genetics / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007420:Intestine, Large / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000941:Antigens; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell; C486171:Tap1 protein, mouse; D054353:Perforin; D051960:GTP-Binding Protein alpha Subunit, Gi2; C498016:Gnai2 protein, mouse