Superantigens have been implicated in the pathogenesis of type I diabetes and other immune-mediated diseases. We therefore tested the hypothesis of an abnormal reactivity of the immune system toward bacterial superantigens during the prediabetic phase. For this purpose, splenocytes from NOD (H-2g7) mice were exposed to two well-characterized superantigens: Staphylococcal aureus enterotoxin-B (SEB) and toxic shock syndrome toxin-1 (TSST-1). Cells from BALB/c (H-2d) and C57BL/6 (H-2b) mice as well as those from NON (H-2non) and NOR (H-2g7) mice were used as controls. After 72 h of co-culture with the superantigens or the mitogen concanavalin A (Con A), proliferative response and mitochondrial activity were determined. In the culture supernatants, the cytokines γ-interferon (IFN-γ) and interleukin 10 (IL-10) were measured. Striking similarities between NOD cells and major histocompatiblity complex (MHC)-identical NOR cells could be observed with regard to a low proliferative and mitochondrial response to SEB, accompanied by a normal response to TSST-1 and Con A, respectively. In addition, only NOD and NOR spleen cells were low producers of the T-helper 1 (Th1) cytokine IFN-γ in response to SEB. Conversely, abnormally high IFN-γ levels were induced by TSST-1 in NOD and NOR spleen cells. The cytokine response to Con A was also biased toward IFN-γ in both NOD and NOR. Since IFN-γ and IL-10 are crucial disease-promoting or -protecting mediators in prediabetic NOD mice, superantigens may affect pathogenesis by acting on the Th1/Th2 cytokine balance. The low responder status toward SEB in NOD spleen cells may be of pathogenetic relevance in view of recent findings that the insulin B-chain also interacts with the SEB binding site on MHC class II molecules. In conclusion, we show here that immune cells from mice with a diabetes-associated MHC type respond differently to common environmental superantigens than do immune cells from control strains.
MHC Class II–Dependent Abnormal Reactivity Toward Bacterial Superantigens in Immune Cells of NOD Mice
APC, antigen-presenting cell; Con A, concanavalin A; ELISA, enzymelinked immunosorbent assay; IFN, interferon; IL, interleukin; mAb, monoclonal antibody; MHC, major histocompatibility complex; PBS, phosphatebuffered saline; SEB, Staphylococcal aureus enterotoxin B; TCR, T-cell receptor; Th, T-helper; TSST-1, toxic shock syndrome toxin-1.
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J Radons, V Burkart, H Kolb; MHC Class II–Dependent Abnormal Reactivity Toward Bacterial Superantigens in Immune Cells of NOD Mice. Diabetes 1 March 1997; 46 (3): 379–385. https://doi.org/10.2337/diab.46.3.379
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