title: Impaired Bacillus Calmette-Guérin cellular immune response in HIV-exposed, uninfected infants.
abstract: OBJECTIVE
  To evaluate cell-mediated immune response to Bacillus Calmette-Guérin (BCG) vaccination in uninfected, HIV-1-exposed infants, comparing it with unexposed children.
  
  
  METHODS
  It is designed as a cross-sectional study.
  
  
  METHODS
  BCG-specific lymphoproliferation and T-cell subsets (CD4(+), CD8(+) and TCR γδ(+)) by flow cytometry and interleukin-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) concentration by ELISA were analyzed in HIV-exposed and unexposed infants. Whole blood lymphocyte immunophenotyping and blood counts were performed in exposed children. Nonparametric tests were used (P < 0.05).
  
  
  RESULTS
  Given the ontogeny of the immune system, exposed infants were separated into three groups according to age: exposed 1 (E1, aged 6.1-8.8 months), E2 (aged 9.1-17.1 months) and E3 (aged 18.1-26.3 months). Unexposed infants (UE group) and E1 were matched for age. Cell proliferation was not different among the three exposed groups, neither for BCG nor for phytohemagglutinin (PHA)-stimulated cultures. Furthermore, BCG-stimulated lymphoproliferation was reduced in the E1 group in comparison with the UE group. T-lymphocyte subpopulations also showed differences, with the youngest HIV-exposed groups (E1 and E2) showing a predominant proliferation of CD4(+) T cells in cultures with BCG, whereas E3 and UE groups had a robust γδ(+) T-cell expansion. There was lower IFN-γ concentration in the samples from E1 group in comparison with all of the other groups. The unexposed infants showed higher TNF-α concentration in cultures with BCG and PHA in comparison with E1 group.
  
  
  CONCLUSIONS
  BCG-specific T-cell proliferation was reduced in HIV-exposed uninfected infants and IFN-γ concentration was lower in younger exposed infants, showing a delay in immune system maturation of HIV-exposed infants.
authors.affiliation: Center for Pediatrics Investigation, Pediatrics Department, State University of Campinas Medical School - UNICAMP, Campinas, Sao Paulo, Brazil.
authors.forename: Taís N
authors.initials: TN
authors.lastname: Mazzola
authors.forename: Marcos T N
authors.initials: MT
authors.lastname: da Silva
authors.forename: Beatriz M
authors.initials: BM
authors.lastname: Abramczuk
authors.forename: Yara M F
authors.initials: YM
authors.lastname: Moreno
authors.forename: Simone C B S
authors.initials: SC
authors.lastname: Lima
authors.forename: Tatiane Q
authors.initials: TQ
authors.lastname: Zorzeto
authors.forename: Andréa S Z
authors.initials: AS
authors.lastname: Passeto
authors.forename: Maria M S
authors.initials: MM
authors.lastname: Vilela
mesh_terms: D001500:BCG Vaccine / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007371:Interferon-gamma / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D001500:BCG Vaccine; D015415:Biomarkers; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma