Functional impairment of regulatory T cell in multiple low dose streptozotocin induced murine diabetes (P3099)

Abstract Despite intense research on the role of the regulatory T cells (Treg), the kinetics of regulatory T cells in the early development of T1D is still not clear. We have examined the proportions of CD4+CD25+Foxp3+ regulatory T (Treg) cells and CD4+ T helper (Th) cells at close intervals in the multiple low dose streptozotocin (MLDSTZ) murine diabetes model using flow cytometry, PCR and immunostaining. The Foxp3 mRNA levels were elevated in the spleen, pancreas and PDLNs of MLDSTZ treated mice. Foxp3 immunostaining in pancreas and spleen suggested that the infiltration of Treg cells increased in pancreas and spleen of MLDSTZ treated mice. The proportions of CD4+CD25+FoxP3+ Treg cells increased in MLDSTZ treated mice from day 7 in pancreatic draining lymph nodes (PDLNs) and day 21 in spleen. The proportions of CD4+ Th cells in MLDSTZ treated mice decreased on day 7 but increase from day 10, at which time the numbers of Tregs increased suggesting that the increase in Tregs fail to control the ongoing immune insult. Impaired mRNA expression levels of IL-35 and IL-10 in PDLNs and spleen of MLDSTZ suggest a functional impairment of the Tregs. Elevated IL-17 mRNA level in spleen of MLDSTZ mice on day 21 further provide evidence of a functional defect in the Tregs. In conclusion Tregs are upregulated in the development of MLDSTZ. However, the upregulation does not protect from hyperglycemia possibly because of a functional deficiency in the Treg population in MLDSTZ treated mice.