Enhancement of CD4(+) T cell response and survival via coexpressed OX40/OX40L in Graves' disease.
OX40/OX40L pathway plays a very important role in the antigen priming T cells and effector T cells. In the present study, we aimed to examine the involvement of OX40/OX40L pathway in the activation of autoreactive T cells in patients with Grave's disease (GD). We found that OX40 and OX40L were constitutively coexpressed on peripheral CD4(+) T cells from GD patients using flow cytometry analysis. The levels of OX40 and OX40L coexpression on CD4(+) T cells were shown to be correlated with TRAbs. Cell proliferation assay showed that blocking OX40/OX40L signal inhibited T cell proliferation and survival, which suggested that OX40/OX40L could enhance CD4(+) T cell proliferation and maintain their long-term survival in GD by self-enhancing loop of T cell activation independent of APCs. Confocal microscopy and coimmunoprecipitation analysis further revealed that OX40 and OX40L formed a functional complex, which may facilitate signal transduction from OX40L to OX40 and contribute to the pathogenesis of GD.
Department of Immunology, Medical College of Soochow University, Suzhou, Jiangsu, China.
Qin
Q
Wang
Department of Endocrinology, No. 1 Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Bi-Min
BM
Shi
Department of Pathology, Medical College of Soochow University, Suzhou, Jiangsu, China.
Fang
F
Xie
Department of Immunology, Medical College of Soochow University, Suzhou, Jiangsu, China.
Zhao-Yang
ZY
Fu
Department of Immunology, Medical College of Soochow University, Suzhou, Jiangsu, China.
Yong-Jing
YJ
Chen
Department of Immunology, Medical College of Soochow University, Suzhou, Jiangsu, China.
Jing-Nan
JN
An
Department of Immunology, Medical College of Soochow University, Suzhou, Jiangsu, China.
Yu
Y
Ma
Clinical Immunology Research Laboratory of Jiangsu Province, No. 1 Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Cui-Ping
CP
Liu
Department of Immunology, Medical College of Soochow University, Suzhou, Jiangsu, China.
Xue-Kun
XK
Zhang
Clinical Immunology Research Laboratory of Jiangsu Province, No. 1 Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Stem Cell Research Laboratory of Jiangsu Province, China. Electronic address: xueguangzh@126.com.
Xue-Guang
XG
Zhang
D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D005260:Female; D006111:Graves Disease / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D053278:OX40 Ligand / Q000378:metabolism*; D053262:Receptors, OX40 / Q000378:metabolism*; D011989:Receptors, Thyrotropin / Q000276:immunology; D015854:Up-Regulation
D001323:Autoantibodies; D053278:OX40 Ligand; D053262:Receptors, OX40; D011989:Receptors, Thyrotropin; C505716:TNFRSF4 protein, human
Coexpression; Graves' disease; OX40/OX40L; T cell activation