Title |
Dynamic Perturbations of CD4 and CD8 T Cell Receptor Repertoires in Chronic Hepatitis B Patients upon Oral Antiviral Therapy
|
---|---|
Published in |
Frontiers in immunology, September 2017
|
DOI | 10.3389/fimmu.2017.01142 |
Pubmed ID | |
Authors |
Ying Xu, Yu Liu, Miaoxian Zhao, Yunqing Chen, Cantao Xie, Mingxing Gong, Haohui Deng, Xueying Li, Jian Sun, Jinlin Hou, Hongkai Wu, Zhanhui Wang |
Abstract |
Long-term treatment with nucleos(t)ide analogs (NUCs) can improve the antiviral T cell response in chronic hepatitis B (CHB) patients. Whether and to what extent the T cell response is improved by NUCs in the early stage leading to hepatitis B e antigen (HBeAg) seroconversion remain to be clarified. A total of 22 CHB patients undergoing 2-year telbivudine-based therapy were enrolled, including 10 exhibiting a complete response (CR) and 12 exhibiting a non-complete response (NCR) according to HBeAg seroconversion at week 52. Peripheral CD4(+) and CD8(+) T cells were sorted at baseline, weeks 12, and 24. The T cell receptor β chain (TCRβ) complementarity-determining region 3 was analyzed by unbiased high-throughput sequencing. Compared with NCR group, patients in CR group had a much lower percentage of persistent clonotypes (P < 0.001) but remarkably higher percentages of new and expanded clonotypes (P < 0.05) between any two time points for both CD4 and CD8 subsets. The CD4 T cells exhibited a stronger response than CD8 population in the patients. The number of new and expanded clonotypes was inversely associated with the decline of viral antigen. In conclusion, NUC-based therapy induces a broad and vigorous T cell response with rapid decline of antigenemia during the early stage of treatment. A broad T cell expansion is crucial for HBeAg seroconversion. Our findings suggest that the potent suppression of hepatitis B virus replication by NUC monotherapy complemented with additional immunomodulatory strategies may increase the likelihood of a functional cure for CHB in the future. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 11 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Doctoral Student | 3 | 27% |
Student > Bachelor | 2 | 18% |
Student > Master | 2 | 18% |
Researcher | 1 | 9% |
Professor > Associate Professor | 1 | 9% |
Other | 0 | 0% |
Unknown | 2 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 3 | 27% |
Biochemistry, Genetics and Molecular Biology | 2 | 18% |
Immunology and Microbiology | 2 | 18% |
Nursing and Health Professions | 1 | 9% |
Agricultural and Biological Sciences | 1 | 9% |
Other | 0 | 0% |
Unknown | 2 | 18% |