T-lymphocyte requirement for diabetes in RT6-depleted diabetes-resistant BB rats.
Diabetes-prone (DP) BB rats develop spontaneous autoimmune insulin-dependent diabetes mellitus (IDDM). The cell populations involved in the expression of diabetes are not precisely known but probably include natural killer (NK) cells, macrophages, and T lymphocytes. Because the DP rat has few lymphocytes of the CD5+/CD+ phenotype, cytotoxic T lymphocytes (Tc) are not believed to be important in the process. Diabetes-resistant (DR) BB rats that are depleted of RT6+ T lymphocytes also become diabetic and provide an additional model of IDDM. We report that diabetes in DR rats depleted of RT6+ T lymphocytes is prevented by the concomitant depletion of either the CD5+ or the CD8+ population. In contrast, coadministration of anti-asialogangliosideM1 (alpha-ASGM1), an antiserum that principally recognizes NK cells, failed to prevent hyperglycemia in RT6-depleted rats. We propose that the initiation of diabetes in both DP and RT6-depleted DR rats is T-lymphocyte dependent. However, the final common pathway leading to autoimmune beta-cell destruction in IDDM may be different in these models. The RT6-depleted DR rat requires a cell that is sensitive to anti-CD8 (possibly a Tc), whereas the DP rat requires an anti-ASGM1-sensitive cell.
Woda
B A
BA
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655.
Handler
E S
ES
Greiner
D L
DL
Reynolds
C
C
Mordes
J P
JP
Rossini
A A
AA
D036002:ADP Ribose Transferases; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology; D018956:CD5 Antigens; D016827:CD8 Antigens; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology*; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008562:Membrane Glycoproteins; D010641:Phenotype; D051381:Rats; D011913:Rats, Inbred BB; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018956:CD5 Antigens; D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D008562:Membrane Glycoproteins; D036002:ADP Ribose Transferases; C090163:Art2b protein, rat