Forced Expression of Programmed Death-1 Gene on T Cell Decreased the Incidence of Type 1 Diabetes

Abstract

Programmed death 1 (PD 1) is a co inhibitory receptor of the CD28/CTLA 4 family which is expressed on activated T cells and inhibits T cell activation after binding to PD ligands In animal models, PD 1 regulates autoimmune disease and induces tolerance in pancreas In this study the effects of PD 1 on type 1 diabetes were examined using PD 1 transgenic mice (Tg) The incidence of autoimmune diabetes induced by multiple low dose of streptozotocin (STZ) was reduced in PD 1 Tg mice Although the expression of CTLA 4, PD 1 and FoxP3, which are inhibitory molecules of activated T cells, is reduced only on STZ injected wild type (WT) mice, CD4, CD8 and regulatory T cell populations were not changed in all experimental groups When splenocytes were re stimulated in ex vivo, the production of IL 2 and IFN gamma and the T cell proliferation were increased in all STZ injected mice, but the increment rate was less in PD 1 Tg groups Interestingly, macrophages were observed in splenocytes of STZ injected PD 1 Tg at somewhat lower level than macrophage in diabetic wild type mice In this research, we found out that total numbers of T cell in the experimental groups are not changed, but T cell function is changed, and FoxP3 expression is decreased in pancreas and spleen of diabetes induced groups Macrophage frequency might also affects on type 1 diabetes Although more experimental evidence needs to be provided, these results suggest that ligation of PD 1 and PD L1/2 may have an effect on macrophages as well as does T cells