Kinetics of immune cell responses in the multiple low-dose streptozotocin mouse model of type 1 diabetes.

Abstract

In type 1 diabetes (T1D), the insulin‐producing β cells are destructed by immune mechanisms. It has been hypothesized that the very first immune response in T1D onset comes from innate immune cells, which further activates the adaptive immune cells to attack the islets. Despite intensive research on characterization of islet‐infiltrating immune cells, the kinetics of different immune cells in multiple low‐dose streptozotocin (MLDSTZ)‐induced T1D mouse model is still much unclear. Therefore, we investigated the proportions of innate immune cells such as neutrophils, dendritic cells (DCs), plasmacytoid dendritic cells (pDCs), macrophages, natural killer (NK) cells, and adaptive immune cells (T and B lymphocytes) in thymi, pancreatic‐draining lymph nodes, and spleens of MLDSTZ mice on days 3, 7, 10, and 21 after the first injection of STZ by flow cytometry. The proportions of DCs and B cells were increased from day 3, while the proportions of B‐1a lymphocytes and interferon‐γ+ cells among NK cells were increased, but NK cells were decreased on day 10 in MLDSTZ‐treated mice, illustrating that the initial immune response is induced by DCs and B cells. Later, the proportions of T helper 1 and cytotoxic T cells were increased from day 7, suggesting that the innate immune cells precede adaptive immune cell response in MLDSTZ mice. Altogether, our data demonstrate a possible sequence of events regarding the involvement of DCs, pDCs, NK cells, B‐1a lymphocytes, B, and T cells at the early stage of T1D development.