Purpose: The TIM family comprises of eight genes in the mouse, three of which are conserved in humans (TIM-1, TIM-3, and TIM-4). Previous studies have revealed the relationships between Tim3+ Tregs and autoimmune disease. There was little study about the expression of Tim1 and Tim4 surface molecules on Tregs. We evaluated the frequency of the Tim1+Tregs and Tim4+Tregs in type 1 diabetes (T1D) in the present study.
Methods: A total of 28 patients with T1D and 14 gender-, age-, and ethnically matched healthy volunteers were recruited. PBMCs from these individuals were isolated and analyzed by flow cytometry. Splenocytes from mice were also analyzed by flow cytometry.
Results: There is no difference in the frequency of Treg cells in peripheral blood isolated from T1D patients. Tim1 on CD4+CD25+ T cells decreased significantly in PBMC of patients with T1D(1.19 ± 0.17% vs 2.78 ± 0.38%, 95% CI:0.87-2.31, P < 0.0001), while expression of Tim4 on CD4+CD25+ T cells in PBMC was less frequent in patients with T1D than healthy people(3.0 ± 0.39% vs 6.25 ± 1.08%, 95% CI:1.08-5.43, P = 0.0044). The frequencies of CD4+CD25+Tim1+ T cells and CD4+CD25+Tim4+ T cells also decreased in spleen of hyperglycemic NOD mice. There were no significant correlations between CD4+CD25+Tim1+T-cells, CD4+CD25+Tim4+T-cells and any clinical features such as age, HbA1c, Fasting C-peptide, diabetic autoantibodies, disease duration, total cholesterol, LDL, HDL, and TG.
Conclusions: It is the first report of the expression of Tim1 and Tim4 molecules on Treg cells in T1D in the present study. We also presented evidence that the frequencies of Tim1+Tregs and Tim4+Tregs decreased significantly in both type 1 diabetic patients and hyperglycemic NOD mice. However, the specific functions of Tim1+Tregs and Tim4+Tregs are still unclear.