Modulation of low-dose streptozotocin-induced diabetes in mice by administration of antibodies to I-A, I-E and I-J determinants.
In male mice of strains C3H and C57BL/6 an experimental immune-mediated diabetes can be induced by multiple low doses of streptozotocin. The delay and partial suppression of hyperglycaemia after anti-I-A monoclonal antibody administration was dose dependent. Even saturation levels of anti-I-A did not cause complete protection from diabetes development. Administration of anti-I-E monoclonal antibody also significantly delayed the onset of hyperglycaemia. Surprisingly, the combined treatment with anti-I-A and anti-I-E did not result in better protection from diabetes. Thus, there is an I-A and I-E independent component of the disease. Furthermore, there is no restriction to either I-A or I-E. Anti-I-A was only effective when given at the beginning of the experiment, which implies that I-A molecules have a primary function during the induction of diabetes. The contribution of I-J to the disease process is different. Administration of a polyspecific alloantiserum to I-J almost completely prevented hyperglycaemia. Injections of monospecific antibodies to I-J determinants enhanced hyperglycaemia, especially when given after the induction of diabetes. This indicates that I-J is involved in initial as well as in later stages of the disease process.
Kiesel
U
U
Diabetes Research Institute, University of Düsseldorf, FRG.
Oschilewski
M
M
Taniguchi
M
M
Kolb
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006943:Hyperglycemia / Q000517:prevention & control; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; C043911:I-J-antigen