Effects of Autologous Immunotherapy on Islet Metabolism and T Cell Immunity in Type 2 Diabetic Rabbits

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disease. Increasing evidence suggests that persistent inflammation and autoimmune mechanisms play a critical role in its pathogenesis. METHODS: T2DM was induced in rabbits through a combination of a high-sugar, high-fat diet and streptozotocin (STZ) administration. The study included three groups: control, T2DM, and T2DM + autologous T cell immunotherapy (ATIM). Individualized ATIM was prepared by heat shock treatment of peripheral blood after erythrocyte removal. Rabbits in the ATIM group received intradermal injections of 0.36 mL ATIM in the thigh every two days. Blood glucose, glycated serum protein (GSP), glycogen synthase (GS), glycogen synthase kinase-3β (GSK3β), T cell subsets, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) levels were measured. RESULTS: ATIM treatment reduced blood glucose and GSP levels, with a trend toward improved glucose tolerance. Compared with the T2DM group, ATIM-treated rabbits exhibited more preserved liver morphology and increased GS expression. The ratio of phosphorylated GSK3β to total GSK3β was decreased. Immunologically, ATIM increased the proportion of CD4+ T cells, decreased IFN-γ levels, and increased IL-10 levels. DISCUSSION: ATIM enhanced GS expression, promoted CD4+ T cell responses, and suppressed pro-inflammatory cytokines in T2DM rabbits, potentially contributing to improved blood glucose control and protection of islet function. CONCLUSION: These findings suggest that ATIM ameliorates T2DM through synergistic regulation of metabolic pathways and immune balance, supporting its potential as a therapeutic approach targeting both metabolic and immune dysfunction in T2DM.