Forced expression of programmed death-1 gene on T cell decreased the incidence of type 1 diabetes.
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.
Chung-Ang University, Seoul, Korea.
Tae Joon
TJ
Won
Yu Jin
YJ
Jung
Seok Joong
SJ
Kwon
Yoon Jeong
YJ
Lee
Do Ik
DI
Lee
Hyeyoung
H
Min
Eon Sub
ES
Park
Seong Soo
SS
Joo
Kwang Woo
KW
Hwang
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism; D060890:B7-H1 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control*; D015870:Gene Expression; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D060908:CTLA-4 Antigen; C498919:Cd274 protein, mouse; C556707:Ctla4 protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma