Staphylococcal enterotoxin-activated spleen cells passively transfer diabetes in BB/Wor rat.
BB/Wor rats develop spontaneous autoimmune diabetes similar to human insulin-dependent diabetes mellitus. A T-cell-mediated pathogenesis for BB/Wor diabetes is indicated because disease is prevented by neonatal or adult thymectomy and treatment of diabetes-prone rats with monoclonal antibodies directed against CD5 or CD8 T-cell surface markers. Disease can be adoptively transferred with injections of concanavalin A-activated spleen cells from either acutely diabetic or RT6.1 T-cell-depleted diabetes-resistant BB/Wor rats. We used microbial superantigens to stimulate spleen cells from RT6.1 T-cell-depleted diabetes-resistant rats and demonstrated that such cells activated with staphylococcal enterotoxins (SEs) can also transfer diabetes. The diabetogenic effector T cells are readily activated by SEA, SEC3, and SEE, whereas SEB- and SEC2-activated cells are far less effective in the adoptive transfer of diabetes. These results demonstrate that microbial superantigens are capable of activating self-reactive and diabetes-inducing T cells in vitro in the BB/Wor rat. Ubiquitous microorganisms may be the environmental trigger for autoimmunity in susceptible individuals.
Ellerman
K E
KE
University of Massachusetts Medical School, Department of Pathology, Worcester 01655.
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D036002:ADP Ribose Transferases; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000945:Antigens, Differentiation, T-Lymphocyte; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D004768:Enterotoxins / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D006649:Histocompatibility Antigens / Q000032:analysis; D016219:Immunotherapy, Adoptive; D008562:Membrane Glycoproteins; D010179:Pancreas / Q000473:pathology; D051381:Rats; D011913:Rats, Inbred BB; D013154:Spleen / Q000187:drug effects / Q000473:pathology*; D013211:Staphylococcus aureus / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000601:surgery; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D004768:Enterotoxins; D058851:GPI-Linked Proteins; D006649:Histocompatibility Antigens; D008562:Membrane Glycoproteins; D036002:ADP Ribose Transferases; C449301:ART1 protein, human; C090163:Art2b protein, rat