Forced expression of programmed death-1 gene on T cell decreased the incidence of type 1 diabetes

• Published in: Archives of pharmacal research 2010, 33(11), , pp.1825-1833
• Main Authors: Won, Tae Joon, Jung, Yu Jin, Kwon, Seok Joong, Lee, Yoon Jeong, Lee, Do Ik, Min, Hyeyoung, Park, Eon Sub, Joo, Seong Soo, Hwang, Kwang Woo
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, Surface - genetics; Antigens, Surface - metabolism; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; B7-1 Antigen - genetics; B7-1 Antigen - metabolism; B7-H1 Antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CTLA-4 Antigen; Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - prevention & control; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - prevention & control; Gene Expression; Immune Tolerance; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-2 - immunology; Interleukin-2 - metabolism; Lymphocyte Activation; Macrophages; Male; Medicine; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peptides - genetics; Peptides - metabolism; Pharmacology/Toxicology; Pharmacy; Programmed Cell Death 1 Ligand 2 Protein; Programmed Cell Death 1 Receptor; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-010-1115-3

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.