title: Induction ofIL21in Peripheral T Follicular Helper Cells Is an Indicator of Influenza Vaccine Response in a Previously Vaccinated HIV-Infected Pediatric Cohort.
abstract: HIV-infected patients of all ages frequently underperform in response to seasonal influenza vaccination, despite virologic control of HIV. The molecular mechanisms governing this impairment, as well as predictive biomarkers for responsiveness, remain unknown. This study was performed in samples obtained prevaccination (T0) from HIV-infected children who received the 2012-2013 seasonal influenza vaccine. Response status was determined based on established criterion for hemagglutination inhibition titer; participants with a hemagglutination titer ≥1:40 plus a ≥4-fold increase over T0 at 3 wk postvaccination were designated as responders. All children had a history of prior influenza vaccinations. At T0, the frequencies of CD4 T cell subsets, including peripheral T follicular helper (pTfh) cells, which provide help to B cells for developing into Ab-secreting cells, were similar between responders and nonresponders. However, in response to in vitro stimulation with influenza A/California/7/2009 (H1N1) Ag, differential gene expression related to pTfh cell function was observed by Fluidigm high-density RT-PCR between responders and nonresponders. In responders, H1N1 stimulation at T0 also resulted in CXCR5 induction (mRNA and protein) in CD4 T cells andIL21gene induction in pTfh cells that were strongly associated with H1N1-specific B cell responses postvaccination. In contrast, CD4 T cells of nonresponders exhibited increased expression ofIL2andSTAT5genes, which are known to antagonize peripheral Tfh cell function. These results suggest that the quality of pTfh cells at the time of immunization is important for influenza vaccine responses and provide a rationale for targeted, ex vivo Ag-driven molecular profiling of purified immune cells to detect predictive biomarkers of the vaccine response.
authors.affiliation: Miami Center for AIDS Research, University of Miami Miller School of Medicine, Miami, FL 33136.|Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136; and.
authors.forename: Lesley R
authors.identifier: 0000-0002-3720-8361
authors.initials: LR
authors.lastname: de Armas
authors.affiliation: Research Unit in Congenital and Perinatal Infection, Immune and Infectious Diseases Division, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, 00165 Rome, Italy.
authors.forename: Nicola
authors.identifier: 0000-0002-7748-1581
authors.initials: N
authors.lastname: Cotugno
authors.affiliation: Miami Center for AIDS Research, University of Miami Miller School of Medicine, Miami, FL 33136.|Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136; and.
authors.forename: Suresh
authors.initials: S
authors.lastname: Pallikkuth
authors.affiliation: Miami Center for AIDS Research, University of Miami Miller School of Medicine, Miami, FL 33136.|Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136; and.
authors.forename: Li
authors.identifier: 0000-0002-3388-5509
authors.initials: L
authors.lastname: Pan
authors.affiliation: Miami Center for AIDS Research, University of Miami Miller School of Medicine, Miami, FL 33136.|Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136; and.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rinaldi
authors.affiliation: Miami Center for AIDS Research, University of Miami Miller School of Medicine, Miami, FL 33136.|Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136; and.
authors.forename: M Celeste
authors.initials: MC
authors.lastname: Sanchez
authors.affiliation: Miami Center for AIDS Research, University of Miami Miller School of Medicine, Miami, FL 33136.|Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136; and.
authors.forename: Louis
authors.identifier: 0000-0002-8752-7897
authors.initials: L
authors.lastname: Gonzalez
authors.affiliation: Research Unit in Congenital and Perinatal Infection, Immune and Infectious Diseases Division, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, 00165 Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cagigi
authors.affiliation: Research Unit in Congenital and Perinatal Infection, Immune and Infectious Diseases Division, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, 00165 Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.affiliation: Research Unit in Congenital and Perinatal Infection, Immune and Infectious Diseases Division, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, 00165 Rome, Italy.
authors.forename: Paolo
authors.identifier: 0000-0002-3066-4719
authors.initials: P
authors.lastname: Palma
authors.affiliation: Miami Center for AIDS Research, University of Miami Miller School of Medicine, Miami, FL 33136; spahwa@med.miami.edu.|Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136; and.
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D015331:Cohort Studies; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000175:diagnosis* / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011379:Prognosis; D054380:Receptors, CXCR5 / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D015415:Biomarkers; C095085:CXCR5 protein, human; D007252:Influenza Vaccines; D007376:Interleukin-2; D007378:Interleukins; D054380:Receptors, CXCR5; D050799:STAT5 Transcription Factor; D000098546:Interleukin-21