OX40 controls islet allograft tolerance in CD154 deficient mice by regulating FOXP3+ Tregs.
The role of OX40 in the islet allograft tolerance, especially in the absence of CD154 costimulation, remains poorly defined. In the present study, we used CD154 deficient mice to critically examine the role of OX40 in the activation of T effector cells and Foxp3+ Tregs and the effect of blocking OX40 on the induction of islet allograft tolerance. We found that blocking OX40 costimulation in CD154 deficient mice induced donor specific tolerance but stimulating OX40 resulted in prompt islet allograft rejection. We also found that OX40 differentially regulates T effector cells and Foxp3+ Tregs, OX40 signaling mediates proliferation of CD154 deficient T effector cells but blocks the induction and suppressor functions of Foxp3+ Tregs. Our data suggest that the role of OX40 in the induction of islet allograft tolerance involves modifying not only the T effector cells but also the Foxp3+ Tregs in CD154 deficient mice.
Chen
Ming
M
Department of Urology, Nanjing Gulou Hospital, Nanjing University Medical School, Nanjing, China.
Xiao
Xiang
X
Demirci
Gulcin
G
Li
Xian Chang
XC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000172:deficiency*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D053278:OX40 Ligand; D014184:Transplantation, Homologous; D000079424:Tumor Necrosis Factor Inhibitors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D048069:Tumor Necrosis Factors / Q000378:metabolism*
D051858:Forkhead Transcription Factors; C472854:Foxp4 protein, mouse; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C504586:Tnfsf4 protein, mouse; D000079424:Tumor Necrosis Factor Inhibitors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D048069:Tumor Necrosis Factors; D023201:CD40 Ligand