Background: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 ...Background: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.Methods: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.Results: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.Conclusions: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.展开更多
Background:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection.However,it was unknown whether SARS-CoV-2 ...Background:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection.However,it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer(NK)cell response in people living with human immunodeficiency virus(PLWH)and healthy individuals.Methods:Forty-seven PLWH and thirty healthy controls(HCs)inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study.The effect of SARS-CoV-2 vaccine on NK cell frequency,phenotype,and function in PLWH and HCs was evaluated by flow cytometry,and the response of NK cells to SARS-CoV-2 Omicron Spike(SARS-2-OS)protein stimulation was also evaluated.Results:SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH,which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine.However,in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers.Additionally,the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0,4 and 12 weeks,but the percentage of CD16^(+)NK cells in PLWH was significantly higher than that in HCs at 2,4 and 12 weeks after the third dose of vaccine.Interestingly,the frequency of CD16^(+)NK cells was significantly negatively correlated with the proportion of CD107a^(+)NK cells in PLWH at each time point after the third dose.Similarly,this phenomenon was also observed in HCs at 0,2,and 4 weeks after the third dose.Finally,regardless of whether NK cells were stimulated with SARS-2-OS or not,we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs.Conclusions:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells,indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.展开更多
基金supported by Beijing Natural Science Foundation(No.L222068 to Bin Su)the National Natural Science Foundation of China(NSFC,No.82272319 to Hu Wu,and No.81974303 to Bin Su)+3 种基金the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(No.2022-2-018 to Bin Su,and No.2022-1-007 to Tong Zhang)the Climbing the peak(Dengfeng)Talent Training Program of Beijing Hospitals Authority(No.DFL20191701 to Tong Zhang)the Beijing Health Technologies Promotion Program(No.BHTPP202002 to Tong Zhang)Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089).
文摘Background: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.Methods: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.Results: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.Conclusions: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.
基金supported by grants from the National Natural Science Foundation of China(Nos.82272319 and 82072271)Beijing Natural Science Foundation(No.L222068)+4 种基金the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(Nos.2022-2-018 and 2022-1-007)the Climbing the peak(Dengfeng)Talent Training Program of Beijing Hospitals Authority(No.DFL20191701)the Beijing Health Technologies Promotion Program(No.BHTPP202002)Scientific Research Project of Beijing Youan Hospital-CCMU 2022(No.BJYAYY-YN-2022-18)Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089)
文摘Background:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection.However,it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer(NK)cell response in people living with human immunodeficiency virus(PLWH)and healthy individuals.Methods:Forty-seven PLWH and thirty healthy controls(HCs)inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study.The effect of SARS-CoV-2 vaccine on NK cell frequency,phenotype,and function in PLWH and HCs was evaluated by flow cytometry,and the response of NK cells to SARS-CoV-2 Omicron Spike(SARS-2-OS)protein stimulation was also evaluated.Results:SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH,which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine.However,in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers.Additionally,the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0,4 and 12 weeks,but the percentage of CD16^(+)NK cells in PLWH was significantly higher than that in HCs at 2,4 and 12 weeks after the third dose of vaccine.Interestingly,the frequency of CD16^(+)NK cells was significantly negatively correlated with the proportion of CD107a^(+)NK cells in PLWH at each time point after the third dose.Similarly,this phenomenon was also observed in HCs at 0,2,and 4 weeks after the third dose.Finally,regardless of whether NK cells were stimulated with SARS-2-OS or not,we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs.Conclusions:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells,indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.
