Alteration in lymphocyte population and humoral immune response in type 2 diabetic Goto-Kakizaki rats

Aims: Proinflammatory cytokine production by a skewed T cell compartment has been shown to be elevated in patients with type 2 diabetes (T2D). However, it is unknown whether humoral immune response controlled by lymphocytes is altered in T2D. Main methods: Lymphocyte populations and immunoglobulin production were investigated in Goto-Kakizaki (G-K) rat, which is a genetic experimental model for T2D, and Wistar rat as a control. Each lymphocyte population was analyzed using flow cytometry. Immunoglobulin in plasma was measured before and after immunization with ovalbumin. The immunoglobulin subclasses and ovalbumin-specific immunoglobulins were measured by enzyme-immunoassay. Effects of improvement in hyperglycemia of G-K rats by chronic diet restriction on lymphocyte populations were also investigated. Key findings: T/B lymphocyte ratios in blood and spleen from the G-K rats were significantly higher than those from the Wistar rats. The difference in the T/B cell ratio in blood of the G-K and Wistar rats was not affected by the diet restriction and the immunization. The ability of immunoglobulin production in G-K rats was comparable to that in Wistar rats, while the levels of natural IgM and ovalbumin-specific IgG2a were higher in plasma from the G-K rats than in plasma from the Wistar rats. Significance: Since helper T cell type 2 (Th2) is known to regulate the class switch to IgG2a in rats, the results of this study suggest that G-K rats are characterized as immunologically Th2 dominant, resulting in increases in natural IgM and T/B cell ratio. (C) 2012 Elsevier Inc. All rights reserved.