Anti-CD2 monoclonal antibodies prevent spontaneous and adoptive transfer of diabetes in the BB/Wor rat.
We studied the effects of anti-CD2 monoclonal antibodies (MAb) on spontaneous and induced autoimmune diabetes mellitus in diabetes-prone (DP) and diabetes-resistant (DR) BB/Wor rats. In DP rats, all anti-CD2 MAb prevented spontaneous diabetes and the adoptive transfer of diabetes with Con-A--stimulated acute diabetic spleen cells; OX34 prevented Poly I:C induced accelerated onset of diabetes and the adoptive transfer of diabetes with Con-A--stimulated RT6.1+ T cell depleted DR splenocytes. In DP rats, all anti-CD2 MAb except OX53 depleted CD4+ T cells, without depleting natural killer cells or CD8+ T cells. OX34 injected DR rats were profoundly depleted of CD4+ T cells without evidence of decreased CD8+ T cells, but were not protected against the induction of diabetes by RT6.1+ T-cell depletion and Poly I:C injections. We conclude that anti-CD2 MAbs protect against BB/Wor autoimmune diabetes by depleting CD4+ T cells, preventing the activation of effector cells, or by blocking CD2/ligand interaction between effector and target cells.
Department of Pathology, University of Massachusetts Medical School, Worcester.
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000517:prevention & control*; D018801:CD2 Antigens; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D003208:Concanavalin A / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000517:prevention & control*; D005434:Flow Cytometry; D006946:Hyperinsulinism / Q000139:chemically induced; D016219:Immunotherapy, Adoptive; D007267:Injections; D008198:Lymph Nodes / Q000473:pathology; D011070:Poly I-C; D051381:Rats; D011913:Rats, Inbred BB; D011971:Receptors, Immunologic / Q000276:immunology*; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D011971:Receptors, Immunologic; D003208:Concanavalin A; D011070:Poly I-C