A role for CD45RBlow CD38+ T cells and costimulatory pathways of T-cell activation in protection of non-obese diabetic (NOD) mice from diabetes.
Non-obese diabetic (NOD) mice spontaneously develop autoimmune insulin-dependent diabetes mellitus (IDDM). Infection of the animals with mycobacteria, or immunization with mycobacteria-containing adjuvant, results in permanent protection of NOD mice from diabetes and we have recently reported that the phenomenon is associated with increased numbers of interferon-gamma-producing T cells, possessing increased cytotoxic activity, and also with augmented numbers of activated immunoglobulin M-positive (IgM+) B cells. Here, we have investigated whether protection of NOD mice from IDDM was associated with changes on costimulatory pathways of T and B cells, namely CD28/CTLA-4-B7 and CD40-CD40 ligand (CD40L) and we also further characterized protective T helper (Th) cells with regards to the expression of the differentiation markers CD45RB and CD38. We report that Th cells involved in diabetes vaccination of NOD mice by mycobacterial infection seem to belong to CD45RBlo CD38+ phenotype. The protective effect of Mycobacterium avium infection is also associated with increased CD40L and CTLA-4- expressing Th cells and with the generation of a CD40- IgG+ B cells. Our data are consistent with induction by mycobacterial infection of regulatory CD45RBlo CD38+ Th cells with the ability to trigger deletion or anergy of peripheral self-reactive lymphocytes, with shutting down of IgG+ B-cell response. They also implicate a role for IgG+ B cells in the autoimmune aggression of the endocrine pancreas of NOD mice.
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Institute for Molecular and Cell Biology, Department of Anatomy, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Portugal.
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D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D016688:Mice, Inbred NOD; D009162:Mycobacterium avium / Q000276:immunology; D009244:NAD+ Nucleosidase / Q000032:analysis; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1