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Cell-mediated and humoral immune responses of mutant diabetic db+/db+ mice were evaluated using in vivo and in vitro immunological assays. When compared to lean, nondiabetic db+/m+ or m+/m+ mice, db+/db+ mice demonstrated markedly altered in vivo immune responses characterized by a significantly diminished ability to reject allogeneic skin grafts, a markedly diminished capacity to generate cytotoxic cells after sensitization with allogeneic EL-4 lymphoma cells and a significantly enhanced plaque-forming cell response to sheep erythrocytes. In contrast, spleen cells from db+/db+ mice demonstrated only minimal alterations in in vitro responses to mitogens and allogeneic cells and no alteration in their capacity to generate an in vitro plaque-forming cell response. The spleens and thymuses of db+/db+ mice weighed significantly less than organs from db+/db+ mice. In addition, thymuses from db+/db+ mice demonstrated a marked deficiency in in vivo [125I]UdR uptake. These data suggest that the altered metabolic status of the diabetic host influences immune function in vivo possibly due to abnormal function of lymphocyte subpopulations.

Immune response in the mutant diabetic C57BL/Ks-dt+ mouse. Discrepancies between in vitro and in vivo immunological assays.