Effect of thymosin α1 on the function of CD4+CD25+CD127dim/- regulatory T cells in chronic hepatitis B patients

Objective To investigate the effect of thymosin α1 therapy on the function of CD4+CD25+CD127dim/-regulatory T ( Treg) cells in chronic hepatitis B ( CHB) patients. Methods A total of 67 CHB patients who were admitted to Department of Infectious Diseases in Shaanxi Provincial People's Hospital from December 2016 to July 2017 were enrolled, among whom 38 patients received entecavir antiviral therapy ( control group) and 29 received entecavir combined with thymosin α1 for injection ( treatment group) . Peripheral blood mononucleated cells were isolated before and after treatment, and flow cytometry was used to measure the percentage of CD4+CD25+CD127dim/-Treg cells. CD4+CD25+CD127dim/-Treg cells were purified and co-cultured with autologous CD4+CD25-T cells. CCK-8 assay was used to measure cell proliferation, and ELISA was used to measure the levels of cytokines. The t-test was used for comparison of related indices between the two groups, the chi-square test was used for comparison of categorical data. Results In the control group, the percentage of CD4+CD25+CD127dim/-Treg cells was significantly reduced from 12. 32% ± 1. 22% at baseline to 8. 85% ± 2. 18% after 12 weeks of treatment ( t = 4. 579, P = 0. 0005) , while in the treatment group, this value was significantly reduced from 13. 71% ± 2. 32% at baseline to 9.26% ± 2. 30% after 12 weeks of treatment ( t = 4. 803, P = 0. 0003) . The measurement of cytokines was performed for 17 patients in the control group and 21 in the treatment group. After 12 weeks of treatment, the control group showed no significant changes in cell proliferation and levels of cytokines in the co-culture system of Treg and CD4+CD25-T cells; the treatment group had a significant increase in cell count in the co-culture system [ ( 3. 66 ± 0. 95) × 106 vs ( 2. 07 ± 0. 51) × 106, t = 5. 709, P < 0. 0001], as well as significant reductions in the levels of inhibitory cytokines interleukin-10 ( 41. 40 ± 11. 89 pg/ml vs 56. 53 ± 27. 85 pg/ml, t = 2. 639, P = 0. 019) and interleukin-35 ( 122. 9 ± 9. 98 pg/ml vs 130. 0 ± 15. 98 pg/ml, t = 2. 459, P = 0. 028) and significant increases in the levels of antiviral cytokines interferon-α ( 297. 5 ± 83. 56 pg/ml vs 235. 6 ± 67. 72 pg/ml, t = 2. 603, P = 0. 017) and interferon-γ ( 5. 83 ± 0. 85 pg/ml vs 4. 39 ± 0. 95 pg/ml, t = 4. 659, P = 0. 0004) . Conclusion Thymosin α1 can inhibit the level and immunosuppressive function of CD4+CD25+CD127dim/-Treg cells in CHB patients and improve their immune function.