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KMID : 0043320100330111825
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Archives of Pharmacal Research
2010 Volume.33 No. 11 p.1825 ~ p.1833
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Forced expression of programmed death-1 gene on T cell decreased the incidence of type 1 diabetes
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Won Tae-Joon
Jung Yu-Jin
Kwon Seok-Joong
Lee Yoon-Jeong
Lee Do-Ik
Min Hye-Young
Park Eon-Sub
Joo Seong-Soo
Hwang Kwang-Woo
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Abstract
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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-1 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-γ 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.
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KEYWORD
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Autoimmune IDDM, T cell activation, Programmed death-1, Programmed death ligand-1, Programmed death ligand-2
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