Effect of helper and/or cytotoxic T-lymphocyte depletion on low-dose streptozocin-induced diabetes in C57BL/6J mice.
The low-dose streptozocin (STZ) model of diabetes has been reported to involve direct STZ beta-cytotoxicity and/or immunologically mediated beta-cell destruction. Because the T-lymphocyte dependency of such a model is controversial, we further assessed the role of T-lymphocytes by determining the occurrence and magnitude of hyperglycemia as well as the pancreatic insulin contents in both STZ-injected nude C57BL/6J male mice and STZ-injected euthymic C57BL/6J male mice selectively depleted in helper and/or cytotoxic T-lymphocytes with monoclonal antibodies (MoAbs). The effectiveness of MoAb treatment was assessed in lymph node cells by flow-microfluorometry analysis and in spleen cells by concanavalin A stimulation, allospecific cytotoxic T-lymphocyte activity, and T-lymphocyte lymphokine production. Sixteen days after the first STZ injection, hyperglycemia (plasma glucose greater than 200 mg/dl) occurred in significantly fewer helper T-lymphocyte-depleted mice (P less than .005) or helper and cytotoxic T-lymphocyte-depleted mice (P less than .001) than in non-MoAb-treated mice. However, a progressive increase in the number of mice with hyperglycemia ensued in all MoAb-treated groups, and 2 mo after STZ was administered, the prevalence of hyperglycemia, mean plasma glucose levels, and pancreatic insulin contents did not differ significantly from the values obtained in the non-MoAb-treated animals. Similarly, STZ-injected C57BL/6J male nude mice developed hyperglycemia that was associated with a marked decrease in pancreatic insulin contents on a time course comparable with that of STZ-injected euthymic C57BL/6J male mice depleted in helper or in helper and cytotoxic T-lymphocytes by MoAbs.(ABSTRACT TRUNCATED AT 250 WORDS)
Dayer-Métroz
M D
MD
Department of Medicine, University of Geneva, Switzerland.
Kimoto
M
M
Izui
S
S
Vassalli
P
P
Renold
A E
AE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology*; D006943:Hyperglycemia / Q000097:blood / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology
D000911:Antibodies, Monoclonal; D001786:Blood Glucose