Analysis of Suppressor and Non-Suppressor FOXP3+ T Cells in HIV-1-Infected Patients

LOURDES ARRUVITO; JUAN SABATTE; JULIETA PANDOLFI; PLÁCIDA BAZ; LUIS A. BILLORDO; MARIA B. LASALA; HORACIO SALOMÓN; JORGE GEFFNER; LEONARDO FAINBOIM

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2012 vol. 7 p. 52580 - 52588

1932-6203

AbstractRecently, it was shown that peripheral blood FOXP3+CD4+ T cells are composed of three phenotypic and functionallydistinct subpopulations. Two of them having in vitro suppressive effects were characterized as resting Treg cells (rTregs)and activated Treg cells (aTregs). A third subset, identified as FOXP3+ non-Tregs, does not display any suppressor activityand produce high levels of Th1 and Th17 cytokines upon stimulation. In the present study we focus on the characteristics ofthese three subsets of FOXP3+CD4+ T cells in untreated HIV-1-infected patients. We found that the absolute counts ofrTregs, aTregs and FOXP3+ non-Tregs were reduced in HIV-1 patients compared with healthy donors. The relative frequencyof rTregs and aTregs was similar in HIV-1 patients and healthy donors, while the frequency of FOXP3+ non-Tregs wassignificantly higher in HIV-1 patients, reaching a maximum in those patients with the lower values of CD4 counts.Contrasting with the observations made in FOXP3- CD4+ T cells, we did not find a negative correlation between the numberof rTregs, aTregs or FOXP3+ non-Tregs and virus load. Studies performed with either whole PBMCs or sorted aTregs andFOXP3+ non-Tregs cells showed that these two populations of FOXP3+ T cells were highly permissive to HIV-1 infection.Upon infection, FOXP3+ non-Tregs markedly down-regulates its capacity to produce Th1 and Th17 cytokines, however, theyretain the ability to produce substantial amounts of Th2 cytokines. This suggests that FOXP3+ non-Tregs might contributeto the polarization of CD4+ T cells into a Th2 profile, predictive of a poor outcome of HIV-1-infected patients.