HIV directly induces accumulation of functional Treg cells through gp120-CD4 interactions. (A) Exposure of CD4+ T cells to AT-2 HIV increases FOXP3 mRNA expression. CD4+ T cells were cultured in presence of either AT-2 HIVMN or control microvesicles (ves). FOXP3 mRNA RU were calculated after normalization on CD4 mRNA levels. CD4 mRNA levels were not affected by AT-2 HIV exposure (results not shown). Results are expressed as the mean ± SE of data obtained in 7 donors. Asterisks indicate a significant difference by paired t test (*P < .05; **P < .005). (B) Increased expression of Treg-cell markers in AT-2 HIV–exposed T cells. Percentage of cells expressing each marker was determined by FACS. Results represent the mean ± SE of data obtained in 4 donors. Similar results were obtained at day 3 (not shown). (C) AT-2 HIV exposure does not induce CD69 up-regulation. Results represent the mean ± SE of data obtained in 4 donors. (D) sCD4 abrogates AT-2 HIV–mediated FOXP3 increased expression. Results represent the mean ± SE of data obtained in 5 donors at day 5. (E) CD4 engagement by anti-CD4 Ab induces increased FOXP3 mRNA expression. Results represent the mean ± SE of data obtained in 3 donors.
