关键词: HIV-1, CD8⁺T细胞, 增生率, 消亡率

Abstract: Objective To observe the changes associated with proliferation and death of CD8⁺ T cell and its subsets including naive CD8⁺ T-cell (T_N), central memory CD8⁺ T-cell (T_CM),effection memory CD8⁺ T-cell (T_EM) and effection memory CD8⁺ T-cell RA (T_EMRA) in chronic HIV-1 infected patients and healthy controls. Same observations were also carried out according to different CD4⁺ T-cell count in chronic HIV-1 infected patients. Methods Sixteen healthy controls and 23 untreated HIV-1 infected patients whose disease course was over 12 months were enrolled in observation. Flow cytometry tests were carried out after routine staining. CD8⁺ T-cells were divided into four subsets based on CD45RO and CD27 expression. They were T_N(CD45RO-CD27+), T_CM (CD45RO+CD27+), T_EM (CD45RO+CD27-) and T_EMRA(CD45RO- CD27-)respectively. Cell proliferation was studied by measuring expression of the Ki-67 antigen. Cell death was studied by annexin V staining. Cell proliferation and death ratio were compared between HIV-1 chronic infection group and healthy group. Same investigations were conducted among three HIV infected groups which were divided according to CD4⁺ T-cell count at 200/mm³ and 350/mm³ levels. Results The distribution of CD8⁺ T-cell subsets in normal control(n=16) were T_N 34.92%±12.68, T_CM 25.44%±10.36%, T_EM 14.64%±10.58%, and T_EMRA 25.00%±12.59%,respectively. The counterparts in HIV-1 infected group(n=23) were T_N 17.14%±8.03%(t=5.368, P=0.000), T_CM 31.40%±14.02%(t=-1.448, P=0.156), T_EM 20.17%±13.17%(t=-1.393, P=0.172), and T_EMRA 31.48%±15.16%(t=-1.405, P=0.168) respectively. The ratio of proliferating cells in CD8⁺ T-cells were 0.15%±0.09% in healthy control and 1.33%±0.90% in infection group(z=-4.655, P=0.000). The ratio of dying cells in CD8⁺ T-cells were 8.74%±4.73% in healthy control and 24.08%±13.72% in infection group(z=-4.169, P<0.001). There was a statistically significant difference in T_N subset among CD4≤200/mm³ group(n=5), CD4 200~350/mm³ group(n=12) and CD4>350/mm³ group(n=6). But there was no significant difference in proliferation and death ratios among these three groups. Conclusion 1 Compared with healthy control, death and proliferation ratios in CD8⁺ T-cells and its subsets increased dramatically. CD8⁺ T-cells were shifted into high flow-ratio cell cycling. 2 The composite ratio of CD8⁺ T_N subset was dramatically down regulated especially in the CD4<200/mm³ group. The resource of CD8⁺ T-cells T_N subset was exhausted following disease progress.

Key words: HIV-1, CD8⁺ T-cells, proliferation ratio, death ratio