title: Analysis of suppressor and non-suppressor FOXP3+ T cells in HIV-1-infected patients.
abstract: Recently, it was shown that peripheral blood FOXP3+CD4+ T cells are composed of three phenotypic and functionally distinct 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 activity and produce high levels of Th1 and Th17 cytokines upon stimulation. In the present study we focus on the characteristics of these three subsets of FOXP3+CD4+ T cells in untreated HIV-1-infected patients. We found that the absolute counts of rTregs, aTregs and FOXP3+ non-Tregs were reduced in HIV-1 patients compared with healthy donors. The relative frequency of rTregs and aTregs was similar in HIV-1 patients and healthy donors, while the frequency of FOXP3+ non-Tregs was significantly 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 number of rTregs, aTregs or FOXP3+ non-Tregs and virus load. Studies performed with either whole PBMCs or sorted aTregs and FOXP3+ 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, they retain the ability to produce substantial amounts of Th2 cytokines. This suggests that FOXP3+ non-Tregs might contribute to the polarization of CD4+ T cells into a Th2 profile, predictive of a poor outcome of HIV-1-infected patients.
authors.affiliation: Institute of Immunology, Genetics and Metabolism (INIGEM), Clinical Hospital, University of Buenos Aires, National Council for Scientific and Technological Research, Buenos Aires, Argentina.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Arruvito
authors.forename: Juan
authors.initials: J
authors.lastname: Sabatté
authors.forename: Julieta
authors.initials: J
authors.lastname: Pandolfi
authors.forename: Plácida
authors.initials: P
authors.lastname: Baz
authors.forename: Luis A
authors.initials: LA
authors.lastname: Billordo
authors.forename: Maria B
authors.initials: MB
authors.lastname: Lasala
authors.forename: Horacio
authors.initials: H
authors.lastname: Salomón
authors.forename: Jorge
authors.initials: J
authors.lastname: Geffner
authors.forename: Leonardo
authors.initials: L
authors.lastname: Fainboim
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002452:Cell Count; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors