Temporal and spatial characterization of negative regulatory T cells in HIV‐infected/AIDS patients raises new diagnostic markers and therapeutic strategies

Background Negative regulatory T cells (Tregs) not only deplete effector T cells but also inhibit the clearance of HIV during infection, which may allow Tregs to be used as informative diagnostic markers. To facilitate both diagnosis and treatment, a thorough understanding of these regulators by characterizing them on temporal and spatial scales is strongly required. Methods Hundred HIV‐infected/AIDS patients, including 87 males, with an average age of 35.8 years, as well as 20 healthy controls, were enrolled. Flow cytometry was used to analyze CD3+T cells, CD4+T cells, and CD8+T cells to evaluate the immune status of the participants. Then, a group of representative negative regulatory T cells, including CD4+PD‐1+T cells, CD4+PD‐1highT cells, CD8+PD‐1+T cells, and CD4+CD25high Tregs was also analyzed to explore their effects on disease progression and intercorrelation. Results The percentages of CD4+PD‐1+T cells and CD4+CD25highTregs increased in patients with the same ultrahigh significance. Temporally, the patients with both intermediate‐stage and late‐stage disease had higher percentages of CD4+PD‐1+T cells; however, the percentage of CD4+CD25highTregs only increased in the patients with late‐stage disease. In addition, CD4+PD‐1+T cells but not CD4+CD25highTregs were negatively correlated with the absolute CD4+T cell count. Spatially, no correlations between CD4+PD‐1+T cells and CD4+CD25highTregs were observed, which suggests these Tregs function differently during immunosuppression. Conclusions This study characterized negative regulatory T cells in HIV‐infected/AIDS patients at both temporal and spatial scales and found that CD4+CD25+Tregs and CD4+PD‐1+T cells could be used as potential diagnostic markers for identifying different disease stages and monitoring disease progression. At late‐stage (CD4+T cells 500/μl). The percentage of CD4+CD25highTregs in the group of CD4+T cells 500/μl. It reveals that the CD4+PD‐1+T cells increased in patients when their absolute CD4+ is less than 500/μl, while CD4+CD25highTregs only increased when absolute CD4+ count is lower than 500/μL. This new discovery indicated that CD4+CD25highTregs are generated at a later stage of HIV infection, which could be used as a clinical indicator for poor disease status. We