title: Regulatory T cells and chronic immune activation in human immunodeficiency virus 1 (HIV-1)-infected children.
abstract: The function of CD4(+) T cells with regulatory activity (T(regs)) is the down-regulation of immune responses. This suppressive activity may limit the magnitude of effector responses, resulting in failure to control human immunodeficiency virus 1 (HIV-1) infection, but may also suppress chronic immune activation, a characteristic feature of HIV-1 disease. We evaluated the correlation between viral load, immune activation and T(regs) in HIV-1-infected children. Eighty-nine HIV-1-infected children (aged 6-14 years) were included in the study and analysed for HIV-1 plasmaviraemia, HIV-1 DNA load, CD4 and CD8 cell subsets. T(reg) cells [CD4(+)CD25(high)CD127(low) forkhead box P3 (FoxP3(high))] and CD8-activated T cells (CD8(+)CD38(+)) were determined by flow cytometry. Results showed that the number of activated CD8(+)CD38(+)T cells increased in relation to HIV-1 RNA plasmaviraemia (r = 0·403, P < 0·0001). The proportion of T(regs) also correlated positively with HIV-1 plasmaviraemia (r = 0·323, P = 0·002), but correlated inversely with CD4(+) cells (r = -0·312, P = 0·004), thus suggesting a selective expansion along with increased viraemia and CD4(+) depletion. Interestingly, a positive correlation was found between the levels of T(regs) and CD8(+)CD38(+)T cells (r = 0·305, P = 0·005), and the percentage of T(regs) tended to correlate with HIV-1 DNA load (r = 0·224, P = 0·062). Overall, these findings suggest that immune activation contributes to the expansion of T(reg) cells. In turn, the suppressive activity of T(regs) may impair effector responses against HIV-1, but appears to be ineffective in limiting immune activation.
authors: Department of Oncology and Surgical Sciences, Section of Oncology, AIDS Reference Center, Padova, Italy.
authors: R
authors: R
authors: Freguja
authors: K
authors: K
authors: Gianesin
authors: I
authors: I
authors: Mosconi
authors: M
authors: M
authors: Zanchetta
authors: F
authors: F
authors: Carmona
authors: O
authors: O
authors: Rampon
authors: C
authors: C
authors: Giaquinto
authors: A
authors: A
authors: De Rossi
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000096:biosynthesis; D002469:Cell Separation; D002478:Cells, Cultured; D002648:Child; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019562:Viral Load
chemical_list: D015703:Antigens, CD; D004279:DNA, Viral; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors