Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(l...Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(low))or high levels(CD8^(high))on HIV-1 replication inhibition after HIV-1 invasion into individual.Methods:Nineteen patients who had been acutely infected with HIV-1(AHI)and 20 patients with chronic infection(CHI)for≥2 years were enrolled in this study to investigate the dynamics of the quantity,activation,and immune responses of CD3^(+)CD8^(low) T cells and their counterpart CD3^(+)CD8^(high) T cells at different stages of HIV-1 infection.Results:Compared with healthy donors,CD3^(+)CD8^(low) T cells expanded in HIV-1-infected individuals at different stages of infection.As HIV-1 infection progressed,CD3^(+)CD8^(low) T cells gradually decreased.Simultaneously,CD3^(+)CD8^(high) T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed.The classical activation of CD3^(+)CD8^(low) T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage.Meanwhile,activated CD38^(-)HLA-DR^(+)CD8^(low) T cells did not increase in the first month of AHI,and the number of these cells was inversely associated with viral load(r=-0.664,P=0.004)but positively associated with the CD4 T-cell count(r=0.586,P=0.014).Increased programmed cell death protein 1(PD-1)abundance on CD3^(+)CD8^(low) T cells was observed from the 1st month of AHI but did not continue to be enhanced,while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domains(TIGIT)abundance increase was observed in the 12th month of infection.Furthermore,increased PD-1 and TIGIT abundance on CD3^(+)CD8^(low) T cells was associated with a low CD4 T-cell count(PD-1:r=-0.456,P=0.043;TIGIT:r=-0.488,P=0.029)in CHI.Nonetheless,the nonincrease in PD-1 expression on classically activated CD3^(+)CD8^(low) T cells was inversely associated with HIV-1 viremia in the first month of AHI(r=-0.578,P=0.015).Notably,in the first month of AHI,few CD3^(+)CD8^(low) T cells,but comparable amounts of CD3^(+)CD8^(high) T cells,responded to Gag peptides.Then,weaker HIV-1-specific T-cell responses were induced in CD3^(+)CD8^(low) T cells than CD3^(+)CD8^(high) T cells at the 3rd and 12th months of AHI and in CHI.Conclusions:Our findings suggest that CD3^(+)CD8^(low) T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response.Subsequently,CD3^(+)CD8^(low) T-cell number decreased gradually as infection persisted,and their anti-HIV functions were inferior to those of CD3^(+)CD8^(high) T cells.展开更多
基金supported by grants from the National Natural Science Foundation of China(NSFC,81974303)the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(2022-2-018)+7 种基金the Ministry of Science and Technology of China(CPL-1233)the“Climbing the peak(Dengfeng)”Talent Training Program of Beijing Hospitals Authority(DFL20191701 and DFL20181701)the Beijing Health Technologies Promotion Program(BHTPP2020)Beijing Key Laboratory for HIV/AIDS Research(BZ0089 and BZ0373)Beijing Natural Science Foundation(7191004)Beijing Municipal Science and Technology Project(Z211100002521024)the Natural Science Foundation of Capital Medical University(PYZ21126)and the Scientific Research Project of Beijing Youan Hospital(CCMU-2020-BJYAYY-2020YC-01 and CCMU-2021-YNKTXF2021001).
文摘Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(low))or high levels(CD8^(high))on HIV-1 replication inhibition after HIV-1 invasion into individual.Methods:Nineteen patients who had been acutely infected with HIV-1(AHI)and 20 patients with chronic infection(CHI)for≥2 years were enrolled in this study to investigate the dynamics of the quantity,activation,and immune responses of CD3^(+)CD8^(low) T cells and their counterpart CD3^(+)CD8^(high) T cells at different stages of HIV-1 infection.Results:Compared with healthy donors,CD3^(+)CD8^(low) T cells expanded in HIV-1-infected individuals at different stages of infection.As HIV-1 infection progressed,CD3^(+)CD8^(low) T cells gradually decreased.Simultaneously,CD3^(+)CD8^(high) T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed.The classical activation of CD3^(+)CD8^(low) T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage.Meanwhile,activated CD38^(-)HLA-DR^(+)CD8^(low) T cells did not increase in the first month of AHI,and the number of these cells was inversely associated with viral load(r=-0.664,P=0.004)but positively associated with the CD4 T-cell count(r=0.586,P=0.014).Increased programmed cell death protein 1(PD-1)abundance on CD3^(+)CD8^(low) T cells was observed from the 1st month of AHI but did not continue to be enhanced,while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domains(TIGIT)abundance increase was observed in the 12th month of infection.Furthermore,increased PD-1 and TIGIT abundance on CD3^(+)CD8^(low) T cells was associated with a low CD4 T-cell count(PD-1:r=-0.456,P=0.043;TIGIT:r=-0.488,P=0.029)in CHI.Nonetheless,the nonincrease in PD-1 expression on classically activated CD3^(+)CD8^(low) T cells was inversely associated with HIV-1 viremia in the first month of AHI(r=-0.578,P=0.015).Notably,in the first month of AHI,few CD3^(+)CD8^(low) T cells,but comparable amounts of CD3^(+)CD8^(high) T cells,responded to Gag peptides.Then,weaker HIV-1-specific T-cell responses were induced in CD3^(+)CD8^(low) T cells than CD3^(+)CD8^(high) T cells at the 3rd and 12th months of AHI and in CHI.Conclusions:Our findings suggest that CD3^(+)CD8^(low) T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response.Subsequently,CD3^(+)CD8^(low) T-cell number decreased gradually as infection persisted,and their anti-HIV functions were inferior to those of CD3^(+)CD8^(high) T cells.
