Altered regulatory T cell phenotype in latent autoimmune diabetes of the adults (LADA)

Summary Latent autoimmune diabetes of the adults (LADA) accounts for up to 12% of all patients with diabetes. Initially the disease resembles type 2 diabetes (T2D); however, the typical presence of β cell autoantibodies indicates an autoimmune basis of LADA. While dysfunctional regulatory T cells (T regs ) have been implicated in autoimmune diabetes, these cells have been scarcely studied in LADA. The aim of this study was to investigate the frequency and phenotype of circulating T regs in LADA patients early during disease progression. Flow cytometric analysis was performed on whole blood and peripheral mononuclear cells (PBMC) from patients diagnosed with LADA prior to insulin deficiency ( n  = 39) and from healthy volunteers ( n  = 20). Overall, we found the frequency and activation status of peripheral putative T regs to be altered in LADA patients compared to healthy controls. While total T cells and CD4 + T cells expressing high levels of CD25 (CD4 + CD25 hi ) were unchanged, the frequency and total numbers of CD4 + T cells expressing an intermediate level of CD25 (CD4 + CD25 int ) were decreased in LADA patients. Interestingly, the expression of the T reg ‐specific marker forkhead box protein 3 (FoxP3), as well as the activation and memory makers CD69, cytotoxic T lymphocyte associated antigen 4 (CTLA‐4), CCR4 and CD45RO were increased in CD4 + CD25 + T cells of the patients. Our data depict phenotypical changes in T cells of LADA patients that may reflect a derangement in peripheral immune regulation contributing to the slow process leading to insulin‐dependent diabetes in these patients.