title: Increased frequencies of CD8+CD57+T cells are associated with antibody neutralization breadth against HIV in viraemic controllers.
abstract: An effective prophylactic vaccine against HIV will need to elicit antibody responses capable of recognizing and neutralizing rapidly evolving antigenic regions. The immunologic milieu associated with development of neutralizing antibody breadth remains to be fully defined. In this study, we sought to identify immunological signatures associated with neutralization breadth in HIV controllers. We applied an immune monitoring approach to analyze markers of T cell and myeloid cell activation by flow cytometry, comparing broad neutralizers with low- and non-neutralizers using multivariate and univariate analyses.
  
  
  
  Antibody neutralization breadth was determined, and cryopreserved peripheral blood mononuclear cells were stained for T cell and myeloid cell activation markers. Subjects were grouped according to neutralization breadth, and T cell and myeloid cell activation was analyzed by partial least squares discriminant analysis to determine immune signatures associated with high neutralization breadth.
  
  
  
  We show that neutralization breadth in HIV viraemic controllers (VC) was strongly associated with increased frequencies of CD8+CD57+T cells and that this association was independent of viral load, CD4 count and time since HIV diagnosis.
  
  
  
  Our data show elevated frequencies of CD8+CD57+T cells in VC who develop neutralization breadth against HIV. This immune signature could serve as a potential biomarker of neutralization breadth and should be further investigated in other HIV-positive cohorts and in HIV vaccine trials.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
authors.forename: Christine D
authors.initials: CD
authors.lastname: Palmer
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
authors.forename: Marisol
authors.initials: M
authors.lastname: Romero-Tejeda
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.|Division of Infectious Diseases, Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Eileen P
authors.initials: EP
authors.lastname: Scully
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
authors.forename: Ainsley
authors.initials: A
authors.lastname: Lockhart
authors.affiliation: Beth Israel Deaconess Medical Center Boston, MA, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Goldenthal
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
authors.forename: Alicja
authors.initials: A
authors.lastname: Piechocka-Trocha
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.|Harvard Medical School, Boston, MA, USA.|Howard Hughes Medical Institute, Chevy Chase, MD, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: Program in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital Boston, MA, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Lori B
authors.initials: LB
authors.lastname: Chibnik
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jost
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.|Harvard Medical School, Boston, MA, USA; filippos.porichis@emdserono.com.
authors.forename: Filippos
authors.initials: F
authors.lastname: Porichis
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D018959:CD57 Antigens; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D000071497:Immunogenicity, Vaccine; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D014766:Viremia / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D018959:CD57 Antigens; D015483:HIV Antibodies
keywords: HIV; T cells; biomarker; broadly neutralizing antibody; immune monitoring; immune signature; viral load