Study On The Relationship Between T Cell Subtypes And Rapid Progression Of HIV Disease

Objective:Acquired immunodeficiency syndrome?AIDS?is caused by Human immunodeficiency virus infection?HIV?,which mainly manifested as depletion of CD4⁺T cells and expansion of CD8⁺T cells,leading to the loss of human immune function.Without therapy,HIV disease progression varies widely among individuals.Rapid progressors?RPs?,representing 10–15%of HIV infected individuals,manifest more rapid decline in their CD4⁺T cells within a few years of infection.Determining the underlying mechanisms throughout this decline is important to identify prognostic biomarkers and intervention strategies.Determining the numbers of CD4⁺and CD8⁺T cells is essential for monitoring the immune status of HIV infected patients.Furthermore,based on the intensity of CD4and CD8 expression,T cells can be further classified as follows:CD4⁺CD8⁺T cells?double positive,DP?,CD4^-CD8^-T cells?double negative,DN?,CD4⁺CD8^lowT cells,and CD4^-CD8^low T cells.Previous studies showed that the number of DN T cells is negatively correlated with HIV viral load.Increased proportions of DP T cells have been observed during HIV infection and phenotypically behave as cytotoxic T cells.The number of CD4^-CD8^lowow T cells gradually increases and inhibits the cytotoxic activity of other cells.Furthermore,alterations in CD4⁺CD8^lowow T cell levels are inconsistent among HIV patients.Thus,these T cell subtypes play an important role in HIV disease and may affect disease progression.However,the relationship of these T cell subtypes to the rapid progression of HIV disease is not well defined.This study intends to identify the T cell subtypes that associated with the rapid progress of HIV and provides new indicators for the prediction of rapid progress of HIV disease.Methods:Research objects.19 RPs were included in this study.The selection criteria was one year after HIV infection,CD4⁺T cell counts<350 cells/?L,while 21 cases of chronic progressors?CPs?were subjects whose CD4⁺T cell counts remained?500 cells/?L after 1year of infection.All patients were treatment na?ve.Based on the intensity of CD4 and CD8 expression,T cells can be further classified as follows:CD4⁺CD8⁺T cells?double positive,DP?,CD4^-CD8^-T cells?double negative,DN?,CD4⁺CD8^low T cells,and CD4^-CD8^lowT cells.Alterations in these T cell subtypes in early HIV infection?within 120days of infection?between RPs and CPs were measured,and the relationships between these subtypes and HIV disease progression were investigated.In addition,expression of IFN-?in T cell subtypes after PMA stimulation was analyzed by flow cytometry.Results:1.CD4⁺CD8^low T cells,DP T cells,DN T cells and CD4^-CD8^low T cells are all reduced in RPs compared to CPs.We used Loess curve fitting to describe dynamic changes in these subtypes during early HIV infection;found that the absolute number and percentage of CD4⁺CD8^low T cells,DP T cells,DN T cells and CD4^-CD8^low T cells in RPs decreased compared to CPs.2.RPs display significantly decreased CD4⁺CD8^low T cells compared to CPs within 120 days of infection.We compared the number and percentage of T cell subtypes between RPs and CPs at different time points during the early stage of HIV infection;found that both the number and percentage of CD4⁺CD8^lowow T cells are clearly significantly decreased in RPs compared to CPs during the early stages of infection.3.CD4⁺CD8^lowow T cells were associated with CD4⁺T cells and HIV viral load.The baseline counts of CD4⁺CD8^low T cells were positively associated with the baseline counts of CD4⁺T cells,while being negatively correlated with baseline HIV-1 viral loads?P=0.0097and P=0.0186?.Similarly,percentages of baseline CD4⁺CD8^low T cells were positively correlated with the counts of baseline CD4⁺T cells,while being negatively correlated with baseline HIV-1 viral loads?P=0.0210 and P=0.0019?.Furthermore,we found that baseline CD4⁺CD8^low T cell levels were also positively correlated with CD4⁺T cells counts 12months later.These data suggest that CD4⁺CD8^low T cells levels during early HIV infection are associated with HIV disease progression.4.Decreased baseline CD4⁺CD8^lowT cell levels in HIV-infected subjects predict rapid CD4⁺T cell decline.Kaplan-Meier survival analysis indicated that the average time for CD4⁺T cell counts to drop to below 350cells/?L and HIV-1 viral loads to reach 10^4.5 copies/mL in the CD4⁺CD8^low T cell high group was significantly longer than in the low group.In addition,in HIV infected patients,reduced baseline CD4⁺CD8^low T cell percentages with more rapid loss of CD4⁺T cells or with faster increases in viral load.These findings indicate that decreased CD4⁺CD8^low T cell levels during early HIV infection predict rapid disease progression.5.CD4⁺CD8^low T cells are committed to producing IFN-?compared to CD4⁺T cells and CD8⁺T cells.CD4⁺CD8^low T cells secreted significantly more IFN-?after PMA stimulation compared to CD4⁺CD8^-T cells and CD4^-CD8⁺T cells,which may be conducive to the prevention of disease progression.Conclusion:In early stage of HIV-1 infection,CD4⁺CD8^low T cells can predict rapid disease progression.2.CD4⁺CD8^lowT cells produce increased IFN-?,which may be beneficial for preventing disease progression.