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‐1 high T cells, CD8+PD‐1+T cells, and CD4+CD25 high Tregs was also analyzed to explore their effects on disease progression and intercorrelation. Results The percentages of CD4 + PD‐1 + T cells and CD4 + CD25 high Tregs 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 + CD25 high Tregs only increased in the patients with late‐stage disease. In addition, CD4 + PD‐1 + T cells but not CD4 + CD25 high Tregs were negatively correlated with the absolute CD4 + T cell count. Spatially, no correlations between CD4 + PD‐1 + T cells and CD4 + CD25 high Tregs 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.