The Frequency And Clinical Significance Of CD4⁺PD-1⁺,CD8⁺PD-1⁺ T Subsets And CD4⁺CD25^highRegulatory T Cells During The Progression Of HIV Infection

[Aim]The progression of human immunodeficiency virus infection and Acquired Immune Deficiency Syndrome(AIDS)is closely related to the function of the immune system.As an immune checkpoint,programmed death-1(PD-1)is closely related to T cell exhaustion.In chronic viral infections and tumorigenesis,PD-1 is aberrantly over-expressed on CD4+,CD8+T cells and negatively regulates antiviral and antitumor immune responses.CD4+CD25+regulatory T cells(Treg),which are characterized by the expression of forkhead transcription factor P3(Foxp3),also play a significant inhibitory role in the body’s antiviral and antitumor immune response.However,the frequency and clinical significance of CD4+PD-1+,CD8+PD-1+T cell population and CD4+CD25high regulatory T cells in peripheral blood of patients with HIV infection and AIDS are not completely clear.Therefore,this study analyzed the frequency of CD4+PD-1+,CD8+PD-1+ T cells and CD4+CD25high regulatory T cells during HIV infection progression from stage Ⅰ(HIV positive,CD4+T cell absolute number>500),stage Ⅱ(HIV positive,200<CD4+T cell absolute number<500)to stage Ⅲ,which is categorized according to the criteria WS293-2008 based on CD4+T cell count(cell number/mm3).Further,the clinical significance of such immune subsets was investigated.[Methods]The peripheral blood of healthy volunteers and HIV/AIDS patients was collected and the erythrocyte lysate was used to lyse the erythrocyte.The number of CD4+T cells was determined by flow cytometry.The frequency of CD4+PD-1+,CD8+PD-1+ T cells and CD4+CD25high regulatory T cells was measured and analyzed by flow cytometry.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serological markers of HIV infection.Quantitative PCR was used to measure HIV RNA.GraphPad Prism 7.0 software was used for analyzing data.[Results]The results showed that compared with healthy control,the frequency of CD4+T cells in peripheral blood of patients at HIV/AIDS stage Ⅱ and Ⅲ decreased significantly,while that of CD8+T cells in peripheral blood of patients at HIV/AIDS stage Ⅰ,Ⅱ and Ⅲ increased significantly.In the patients with HIV/AIDS,the frequency of CD4+T cells decreased gradually from stage Ⅰ,stage Ⅱ to Ⅲ,while that of CD8+T cells increased gradually.The frequency of CD4+T cells in HIV/AIDS patients was positively correlated with CD4+T cell absolute count,while that of CD8+T cells was negatively correlated with CD4+T cell absolute count.Compared with the healthy control,the frequency of CD4+PD-1+T population in CD4+T cells of patients with HIV/AIDS stage Ⅱ and Ⅲ increased significantly,and was significantly higher than that of patients at stage Ⅰ.The frequency of CD4+PD-1+population in HIV/AIDS patients was negatively correlated with the absolute count of CD4+T cells.Although the frequency of CD8+PD-1+ population in CD8+T cells of HIV/AIDS patients in different stages increased significantly compared with healthy control,but there was no difference between different stages.At the same time,it was found that there was no significant correlation between the frequency of CD8+PD-1+ population and the absolute count of CD4+T cells in HIV/AIDS patients.Compared with the healthy control,the frequency of CD4+CD25high regulatory T cells increased significantly in all stages of HIV/AIDS,but there was no difference between different stages.Simultaneously,the frequency of CD4+CD25high regulatory T cells in HIV/AIDS patients was negatively correlated with the absolute count of CD4+T cells.Further analysis showed that there was no significant correlation between the frequency of CD4+PD-1+ and CD8+PD-1+ population and the proportion of CD4+CD25high regulatory T cells.[Conclusion]The current study substantiated that the frequency of CD4+PD-1+,CD8+PD-1+T cells and CD4+CD25high regulatory T cells increased in HIV/AIDS patients,and revealed that upregulation of PD-1 on CD4+T cells and the increase of Treg frequency were positively correlated with the progress of HIV infection to some extent,suggesting that upregulation of PD-1 on T cells and the increase of Treg frequency may be involved in anti-HIV immune suppression,resulting in the progression of HIV infection.These findings provide potential targets for clinical diagnosis and treatment of HIV infection.