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 480 cells/μl (33–1306) and plasma HIV RNA levels ranged between 3.3 and 5.7 log10 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+CD25high T cells. Results:The frequency of CD4+CD127lowCD25high 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+CD25high 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.

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