Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV Infection, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, China.
Chin Med J (Engl). 2023 Dec 20;136(24):2938-2947. doi: 10.1097/CM9.0000000000002926. Epub 2023 Nov 14.
T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines.
Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose.
Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W.
TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
T 细胞免疫受体含有免疫球蛋白和免疫受体酪氨酸抑制基序结构域（TIGIT），是一种在 T 细胞上表达的抑制性受体，在抗病毒感染和抗肿瘤活性中发挥功能失调的作用。然而，TIGIT 在 T 细胞上的表达是否影响严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）灭活疫苗的免疫效果尚不清楚。
本研究纳入了 45 名接受抗逆转录病毒治疗（ART）超过两年的 HIV 感染者（PLWH）和 31 名健康对照（HCs），所有参与者均接受了第三剂 SARS-CoV-2 灭活疫苗。在第三剂疫苗前（0 周）、第二剂疫苗后 4 周（4 周）和 12 周（12 周），检测了 TIGIT + CD4 + 和 TIGIT + CD8 + T 细胞的数量、激活、亚群比例以及 SARS-CoV-2 特异性免疫反应的幅度。
与 HCs 相比，PLWH 外周血中 TIGIT + CD8 + T 细胞在第三剂灭活疫苗后 12 周时增加，TIGIT + CD8 + T 细胞的免疫激活也增加。在 PLWH 中，TIGIT + CD8 + T 细胞中 T 幼稚（T N ）和中央记忆（T CM ）细胞的比例下降，效应记忆（T EM ）亚群的比例增加。有趣的是，基于激活诱导标记物检测，与 HCs 相比，PLWH 中同时表达 CD137 和 CD69 的 TIGIT + CD8 + T 细胞的比例在 12 周时更高。与 0 周相比，PLWH 中 SARS-CoV-2 特异性 TIGIT + CD8 + T 细胞反应在 12 周时并未增强，而在 HCs 中增强。此外，在所有时间点，PLWH 中 SARS-CoV-2 特异性 TIGIT + CD8 + T 细胞反应均明显弱于 TIGIT - CD8 + T 细胞反应。然而，在 HCs 中，TIGIT + CD8 + T 细胞与 TIGIT - CD8 + T 细胞之间诱导的 SARS-CoV-2 特异性反应的差异在 4 周和 12 周时不显著，除了在 0 周时。
CD8 + T 细胞上的 TIGIT 表达可能会阻碍对 SARS-CoV-2 灭活疫苗加强剂量的 T 细胞免疫反应，这表明对 SARS-CoV-2 感染的抵抗力减弱，尤其是在 PLWH 中。此外，TIGIT 可作为增加 SARS-CoV-2 特异性 CD8 + T 细胞产生的潜在靶点，从而增强疫苗的有效性。
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