[Effects of PEG-IFN-α treatment on the expression of CD⁺161 and PD-1 in CD8⁺ T cells of patients with chronic hepatitis B].

<b>Objective:</b> To investigate and explore the expressional condition and therapeutic role of PD-1 and CD161 in the peripheral blood of patients treated with PEG-IFN-α for chronic hepatitis B (CHB), and their correlation with the degree of decrease in hepatitis B surface antigen (HBsAg). <b>Methods:</b> A retrospective cohort study was conducted. CHB patients who visited the Second Affiliated Hospital of Xi'an Jiaotong University from July 2022 to December 2023 and healthy controls during the same period were included. Peripheral blood samples were collected from the IFN treatment group (31 cases), the non-IFN treatment group (30 cases), and the healthy control group (30 cases). Flow cytometry was used to detect the CD8,⁺ PD-1,⁺ CD161⁺ T lymphocytes and their subpopulations among the three groups. The proportions of cellular subpopulations were compared to analyze intergroup differences using Kruskal-Wallis and Mann-Whitney <i>U</i> tests. The patients in the IFN treatment group were divided into two subgroups, high-and low-level, according to the median levels of PD-1⁺ lymphocytes, CD8⁺PD-1⁺T cells, and CD161⁺ lymphocytes. The magnitude of HBsAg decline was compared between the two groups. <b>Results:</b> The proportions of PD-1⁺ lymphocytes and CD8⁺PD-1⁺T cells in the IFN treatment group were significantly higher than those in the healthy control group and the non-IFN treatment group (<i>P</i><0.001). Moreover, the proportions of PD-1⁺ lymphocytes [IFN treatment group 48 weeks: 24.3 (23.7, 28.0)%, non-IFN treatment group: 12.7 (10.0, 18.5)%, <i>P</i><0.01] and CD8⁺PD-1⁺T cells [IFN treatment group 48 weeks: 29.29 (26.73, 32.98)%, non-IFN treatment group: 17.69 (9.62, 20.68)%, <i>P</i><0.05] were higher in the IFN treatment group than those in the non-IFN treatment group at 48 weeks. The proportion of CD8⁺CD161⁺T cells was significantly lower in patients treated with IFN than in the non-IFN treatment group (<i>P</i><0.05) at 24 and 48 weeks, with no statistically significant difference with the healthy control group (<i>P</i>>0.05). In the IFN treatment group, patients with high levels of PD-1⁺ and CD8⁺ PD1 lymphocytes had a significantly lower HBsAg decline compared to low-level patients, whereas no significant correlation was found between CD161 levels and HBsAg decline [PD-1⁺ lymphocytes: 0.15 (0.02, 0.18) log₁₀ IU/mL <i>vs</i>. 0.32 (0.13, 0.42) log₁₀ IU/mL, <i>P</i><0.01; CD8⁺PD-1⁺T cells: 0.16 (0.03, 0.17) log₁₀ IU/mL <i>vs</i>. 0.34 (0.13, 0.44) log₁₀ IU/mL, <i>P</i><0.05]. <b>Conclusion:</b> The proportions of CD8⁺PD-1⁺T cells and CD8⁺CD161⁺T cells were significantly regulated by PEG-IFN-α therapy in the peripheral blood of patients with CHB, revealing the important role of T cell immune activation status during antiviral treatment. The gradual decline of HBsAg is closely related to the high expression of PD-1, suggesting that PD-1 may be negatively regulated during the process of T cell exhaustion and immunological evasion.