Cell-mediated immunity in chronically diabetic mice.

Abstract

A radioisotopic ear assay for delayed hypersensitivity (DH) to 2,4-dinitrofluorobenzene (DNFB) was used to investigate cellular immune function in chronic alloxan- diabetic C57BI/6 mice. The specific migration of 5-(125I)Iodo-2'-deoxyuridine-labeled monocytes to the site of antigenic challenge was employed to quantitatively measure the OH response. Although both normal and diabetic sensitized mice had a significantly greater DH response than nonsensitized controls, the response of diabetic mice was severely attenuated (23% of normal) The effect of the delayed hypersensitivity response on spleen size was also investigated. In the nonsensitized state the spleens of diabetic mice were approximately 30% smaller than the spleens of normal mice. After sensitization with DNFB, and up to the time of antigenic challenge, the spleens from both diabetic and normal mice increased 2.1-fold in weight. After challenge, however, the diabetic spleen maintained its prechallenged size while the normal spleen increased an additional 30% in weight. When either sensitized normal or diabetic spleen cells were passively transferred to nonsensitized normal recipient mice, a significant DH response was evoked after challenge with DNFB. This response was of equal magnitude after transfer of either the sensitized diabetic or normal spleen cells. The DH response after the passive transfer of spleencells from either normal or diabetic sensitized donors to diabetic recipients was very markedly attenuated and in fact questionably significant when compared with the nonspecific inflammatory response to DNFB. These results indicate that an intact population of DNFB-sensitized cells exists in the diabetic, but that an inhibition of T-lymphocyte or monocyte activity is occurring during the secondary challenge. The chronic hypoinsulinemia, hyperglycemia, and catabolic metabolism of the alloxan-diabetic mouse does not qualitatively alter the immune cellular processes associated with primary sensitization but significantly attenuates the secondary response.