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/microl (33-1306) and plasma HIV RNA levels ranged between 3.3 and 5.7 log10 copies/ml. Suppressive capacity of blood purified CD4CD25 was evaluated in a coculture assay. Fox-p3, IL-2 and IL-10 were quantified by reverse transcriptase (RT)-PCR and intracellular staining of ex vivo and activated CD4+CD25 T cells.


RESULTS
The frequency of CD4CD127CD25 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 CD4CD25 T cells. CD4CD25 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.


CONCLUSIONS
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.
Kared
Hassen
H
INSERM, Unite U841, France.
Lelièvre
Jean-Daniel
JD
Donkova-Petrini
Vladimira
V
Aouba
Albertine
A
Melica
Giovanna
G
Balbo
Michèle
M
Weiss
Laurence
L
Lévy
Yves
Y
D018791:CD4 Lymphocyte Count / Q000379:methods; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008297:Male; D010641:Phenotype; D011446:Prospective Studies; D012367:RNA, Viral / Q000276:immunology* / Q000378:metabolism; D013491:Suppressor Factors, Immunologic / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology; D019562:Viral Load
D053645:Interleukin-2 Receptor alpha Subunit; D012367:RNA, Viral; D013491:Suppressor Factors, Immunologic; D016753:Interleukin-10