HIV-specific regulatory T cells are associated with higher CD4 cell counts in primary infection

Objective: Expansion of regulatory T (Treg) cells has been described in chronically HIV-infected individuals. We investigated whether HIV-suppressive Treg could be detected during primary HIV infection (PHI). Methods: Seventeen patients diagnosed early after PHI (median: 13 days; 1-55) were studied. Median CD4 cell count was 480cells/mu l (33-1306) and plasma HIV RNA levels ranged between 3.3 and 5.7 log(10) copies/ml. Suppressive capacity of blood purified CD4(+)CD25(+) was evaluated in a coculture assay. Fox-p3, IL-2 and IL-10 were quantified by reverse transciptase (RT)-PCR and intracellular staining of ex vivo and activated CD4+CD25(high) T cells. Results: The frequency of CD4(+)CD127(low)CD25(high) T cells among CD4 T cells was lower in patients with PHI compared with chronic patients (n = 19). They exhibited a phenotype of memory T cells and expressed constitutively FoxP3. Similar to chronic patients, Treg from patients with PHI inhibited the proliferation of purified tuberculin (PPD) and HIV p24 activated CD4(+)CD25(-) T cells. CD4+CD25(high) T cells from patients with PHI responded specifically to p24 stimulation by expressing IL-10. In untreated patients with PHI, the frequency as well as HIV-specific activity of Treg decreased during a 24-month follow-up. A positive correlation between percentages of Treg and both CD4 cell counts and the magnitude of p24-specific Suppressive activity at diagnosis of PHI was found. Conclusion: Our data showed that HIV drives Treg, as PHI and these cells persist throughout the course of the infection. A correlation between the frequency of Treg and CD4 T-cell counts suggest that these cells may impact on the immune activation set point at PHI diagnosis. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins