title: CD4+ T-cell activation impairs serogroup C Neisseria meningitis vaccine response in HIV-infected children.
abstract: OBJECTIVE
  To investigate the influence of CD4 T-cell activation and regulatory populations in HIV-infected children antibody response to vaccination with a conjugate C polysaccharide vaccine.
  
  
  METHODS
  CD4 T-cell activation was evaluated by expression of CD38, HLA-DR and CCR5 molecules. Regulatory CD4 T cells (TReg) were characterized as FoxP3CD127CD25 and inducer T cells (TInd) as CD4FoxP3CD25CD39.
  
  
  METHODS
  All patients (n = 36) were HIV-vertically infected, aged 2-17 years-old and were vaccinated with one vaccine injection. Blood samples were obtained before and after immunization to determine bactericidal antibody titers (SBA), CD4 T-cell activation and frequency of TReg and TInd subsets (multiparametric flow cytometry).
  
  
  RESULTS
  Children not-responding (n = 18) to MenC vaccine expressed higher frequency of activated CD4 T cells (HLA-DRCD38CCR5) than responders (n = 18), both before and after vaccination (P < 0.05). A significant higher frequency of TReg was detected in responders compared with nonresponders (P = 0.0001). We also detected an inverse correlation between CD4DRCD38CCR5 (P = 0.01) or CD4DRCD38 (P = 0.02) T cells and TReg cell frequency after vaccination. CD4 T-cell activation negatively correlated (P = 0.006) with postvaccination SBA titers but a positive correlation (P = 0.0001) was detected between TReg cells and SBA. TReg and TInd subsets were inversely correlated (P = 0.04).
  
  
  CONCLUSIONS
  Our findings suggest that higher CD4 T-cell activation leads to poor vaccine response in children living with HIV, which may be associated with a TReg/TInd disequilibrium.
authors.affiliation: aState University of Rio de Janeiro, Department of Microbiology, Immunology and Parasitology, Rio de Janeiro bDivision of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo cInstituto de Puericultura e Pediatria Martagão Gesteira dPreventive Medicine Department, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Lucimar G
authors.initials: LG
authors.lastname: Milagres
authors.forename: Priscilla R
authors.initials: PR
authors.lastname: Costa
authors.forename: Bianca A N
authors.initials: BA
authors.lastname: Santos
authors.forename: Giselle P
authors.initials: GP
authors.lastname: Silva
authors.forename: Aline C
authors.initials: AC
authors.lastname: Cruz
authors.forename: Wânia F
authors.initials: WF
authors.lastname: Pereira-Manfro
authors.forename: Bianca
authors.initials: B
authors.lastname: Ferreira
authors.forename: Daniella M
authors.initials: DM
authors.lastname: Barreto
authors.forename: Ana Cristina C
authors.initials: AC
authors.lastname: Frota
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Cristina B
authors.initials: CB
authors.lastname: Hofer
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
mesh_terms: D000293:Adolescent; D000907:Antibodies, Bacterial / Q000097:blood; D015703:Antigens, CD / Q000032:analysis; D001770:Blood Bactericidal Activity; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D015658:HIV Infections / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000032:analysis
chemical_list: D000907:Antibodies, Bacterial; D015703:Antigens, CD; C584933:CCR5 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006684:HLA-DR Antigens; D022401:Meningococcal Vaccines; D019713:Receptors, CCR5