Production of Autoantibodies in Chronic Hepatitis B Virus Infection Is Associated with the Augmented Function of Blood CXCR5+CD4+ T Cells.
T follicular helper cells (Tfh) provide help to B cells to support their activation, expansion and differentiation. However, the role of Tfh cells in chronic HBV infection is poorly defined. The aim of this research was to examine the function of Tfh cells and whether they are involved in HBV related disease. Blood CXCR5+CD4+T cells and B cells in 85 patients with chronic HBV infection (HBV patients) and health controls (HC) were examined by flow cytometry. The molecule expression in blood CXCR5+CD4+ T cells was detected by real-time PCR. Blood CXCR5+CD4+ T cells and B cells were co-cultured and the production of Ig and cytokines was detected by ELISA. Autoantibodies were detected by indirect immunofluorescence and immunospot assay. We found that blood CXCR5+CD4+ T cells in patients with chronic HBV infection (HBV patients) expressed higher level of activation related molecules and cytokines than that from health controls (HC).In HBV patients, the frequency of blood CXCR5+CD4+ T cells was significantly correlated with serum ALT and AST. We also found that blood CXCR5+CD4+ T cells from HBV patients could induce B cells to secret higher level of immunoglobulin than that from HC. Several autoantibodies, including ANA, ss-A, ss-B, Scl-70, Jo-1, ect, were indeed positive in 65% HBV patients. Among HBV patients, expression of function related molecules was significantly higher in blood CXCR5+CD4+ T cells from patients with autoantibodies than that without autoantibodies. Our research indicated that blood CXCR5+CD4+ T cells from HBV patients were over activated and show augmented capacity to help B cells for antibody secreting, which might correlated with liver inflammation and the production of autoantibodies in extrahepatic manifestations.
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, No.74 Lin Jiang Rd., Yu Zhong District, 400010, Chongqing, People's Republic of China.
Yu
Y
Lei
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, No.74 Lin Jiang Rd., Yu Zhong District, 400010, Chongqing, People's Republic of China.
Tingting
T
Hu
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, No.74 Lin Jiang Rd., Yu Zhong District, 400010, Chongqing, People's Republic of China.
Xiaofei
X
Song
Department of Laboratory Medicine, the Second Affiliated Hospital, Chongqing Medical University, No.74 Lin Jiang Rd., Yu Zhong District, 400010, Chongqing, People's Republic of China.
Hong
H
Nie
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, No.74 Lin Jiang Rd., Yu Zhong District, 400010, Chongqing, People's Republic of China.
Min
M
Chen
Department of Laboratory Medicine, the Second Affiliated Hospital, Chongqing Medical University, No.74 Lin Jiang Rd., Yu Zhong District, 400010, Chongqing, People's Republic of China.
Weixian
W
Chen
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, No.74 Lin Jiang Rd., Yu Zhong District, 400010, Chongqing, People's Republic of China.
Zhi
Z
Zhou
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, No.74 Lin Jiang Rd., Yu Zhong District, 400010, Chongqing, People's Republic of China.
Dazhi
D
Zhang
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, No.74 Lin Jiang Rd., Yu Zhong District, 400010, Chongqing, People's Republic of China.
Huaidong
H
Hu
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, No.74 Lin Jiang Rd., Yu Zhong District, 400010, Chongqing, People's Republic of China.
Peng
P
Hu
Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, the Second Affiliated Hospital, Chongqing Medical University, No.74 Lin Jiang Rd., Yu Zhong District, 400010, Chongqing, People's Republic of China.
Hong
H
Ren
D000328:Adult; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D054380:Receptors, CXCR5 / Q000378:metabolism
D001323:Autoantibodies; D054380:Receptors, CXCR5