Increased Circulating T Follicular Helper Cells Induced via IL-12/21 in Patients With Acute on Chronic Hepatitis B Liver Failure
Authors: Yuanyuan Tian
Bingying Du
Jiaming Teng
Yanan Du
Tingwang Jiang
Rongkun Yin
Wei Cai
Journal: Frontiers in Immunology (2021)
Discipline: IMMUNOLOGY
Keywords: T follicular helper cell; hepatitis B virus-related acute on chronic liver failure; interleukin-12; interleukin-21; pathogenesis.
Affiliations: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Department of Infectious Diseases, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Department of Hematology, Children Hospital, Soochow University, Suzhou, China., Clinical Research Centre, The Affiliated Changshu Hospital of Xuzhou Medical University, Changshu, China.

Abstract:  Objectives: T Follicular helper (Tfh) cells, recognized as a distinct CD4+ T cell subset, mediate the development of long-lived humoral immunity via B cell activation/differentiation. Tfh cells play an important role during hepatic viral infection, but its role in hepatitis B virus-related acute on chronic liver failure (HBV-ACLF) remains to be explored. Materials and methods: The frequency of Tfh cells, serum pro-inflammatory cytokine (IL-12, IL-21, IL-17 and TNF) levels and IgG/M levels were investigated in HBV-ACLF (n = 36), serious chronic hepatitis B (n = 21), moderate chronic hepatitis B patients (n = 32) and healthy control (HC) subjects (n = 10). Results: Circulating Tfh cells were significantly increased in HBV-ACLF patients compared to other groups, correlating well with MELD score. However, the frequency of Tfh cells decreased in ameliorated HBV-ACLF patients. Furthermore, serum IL-12 and IL-21 levels were higher in HBV-ACLF patients, compared to other groups. Naïve CD4+ T cells from HC subjects differentiate into Tfh cells following treatment with HBV-ACLF patients' serum, a process that can be blocked by IL-12/21 neutralizing antibodies. Tfh cells induced by HBV-ACLF patient's serum promoted the proliferation and IgG production of B cells in vitro. Moreover, circulating CD19+ B cells, serum and liver IgG/M levels were significantly higher in HBV-ACLF patients, compared to other groups. Conclusions: Our data demonstrated that there was a high frequency of Tfh cells and high levels of serum IL-12/21 in HBV-ACLF patients. Naïve CD4+ T cells differentiate into Tfh cells in the presence of HBV-ACLF patients' serum rich in IL-12/21, which can be blocked by neutralizing IL-12/21 antibodies. These data may provide useful insights for both clinical and basic research in the treatment of HBV-ACLF. 

Retracted: No

PubPeer comments:
 Dear authors, Could you please provide the original FCS files for Fig.4A-C? Some dot plots contain either identical or highly similar dot pattern. Since not all areas of these plots are identical one can exclude a simple image duplication. However this raises the concern of manipulation. Could you please clarify. ![file] , 
 **ADDENDUM PUBLISHED CONTAINING ORIGINAL FACS DATA** https: www.frontiersin.org articles 10.3389 fimmu.2021.641362 full Thanks to the authors for providing the data, which will be reviewed. ,