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.