Investigation on Proliferation and Death of CD8~+ T-cell and Its Subsets in Chronic HIV-1 Infected Persons

Objective To observe the changes associated with proliferation and death of CD8+ T cell and its subsets including naive CD8+ T-cell(TN),central memory CD8+ T-cell(TCM),effection memory CD8+ T-cell(TEM) and effection memory CD8+ T-cell RA(TEMRA) 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 TN(CD45RO-CD27+),TCM(CD45RO+CD27+),TEM(CD45RO+CD27-) and TEMRA(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 TN 34.92%±12.68,TCM 25.44%±10.36%,TEM 14.64%±10.58%,and TEMRA 25.00%±12.59%,respectively.The counterparts in HIV-1 infected group(n=23) were TN 17.14%±8.03%(t=5.368,P=0.000),TCM 31.40%±14.02%(t=-1.448,P=0.156),TEM 20.17%±13.17%(t=-1.393,P=0.172),and TEMRA 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,P0.001).There was a statistically significant difference in TN subset among CD4≤200/mm3 group(n=5),CD4 200～350/mm3 group(n=12) and CD4350/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+ TN subset was dramatically down regulated especially in the CD4200/mm3 group.The resource of CD8+ T-cells TN subset was exhausted following disease progress.