title: Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma are associated with nonprogressive HIV-1 infection.
abstract: BACKGROUND
  Long-term survival of HIV-1 infected individuals is usually achieved by continuous administration of combination antiretroviral therapy (ART). An exception to this scenario is represented by HIV-1 infected nonprogressors (NP) which maintain relatively high circulating CD4+ T cells without clinical symptoms for several years in the absence of ART. Several lines of evidence indicate an important role of the T-cell response in the modulation of HIV-1 infection during the acute and chronic phase of the disease.
  
  
  RESULTS
  We analyzed the functional and the differentiation phenotype of Nef- and Tat-specific CD8+ T cells in a cohort of HIV-1 infected NP in comparison to progressors, ART-treated seropositive individuals and individuals undergoing a single cycle of ART interruption. We observed that a distinctive feature of NP is the presence of Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma. This population was present in 7 out of 11 NP. CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells were not detected in HIV-1 infected individuals under ART or withdrawing from ART and experiencing a rebounding viral replication. In addition, we detected Nef-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1 infected individuals with untreated progressive disease.
  
  
  CONCLUSIONS
  The novel antigen-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cell population represents a new candidate marker of long-term natural control of HIV-1 disease progression and a relevant functional T-cell subset in the evaluation of the immune responses induced by candidate HIV-1 vaccines.
authors.affiliation: Institute of Virology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors.forename: Claudia J
authors.initials: CJ
authors.lastname: Dembek
authors.affiliation: Institute of Virology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kutscher
authors.affiliation: Human Virology Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.|AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Heltai
authors.affiliation: Clinical Cooperation Group "Immune Monitoring", Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Institute of Virology, Technische Universität München, 81675 Munich, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Allgayer
authors.affiliation: Laboratory of Clinical Immunology, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Biswas
authors.affiliation: Viral Pathogens and Biosafety Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ghezzi
authors.affiliation: Viral Pathogens and Biosafety Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Vicenzi
authors.affiliation: Institute of Virology, Technische Universität München, 81675 Munich, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoffmann
authors.affiliation: Institute of Health Economics and Health Care Management, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Reitmeir
authors.affiliation: Department of Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tambussi
authors.affiliation: Department of Infectious Diseases, Medizinische Poliklinik, Ludwig Maximilians Universität, 80336 Munich, Germany.
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Bogner
authors.affiliation: Human Virology Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Lusso
authors.affiliation: Infektionsmedizinisches Centrum Hamburg ICH, 20146 Hamburg, Germany.
authors.forename: Hans-J
authors.initials: HJ
authors.lastname: Stellbrink
authors.affiliation: "A. Bianchi Bonomi" Haemophilia and Thrombosis Center, University of Milan, 20122 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Santagostino
authors.affiliation: Department of Infectious Diseases, Medizinische Poliklinik, Ludwig Maximilians Universität, 80336 Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vollbrecht
authors.affiliation: Department of Infectious Diseases, Medizinische Poliklinik, Ludwig Maximilians Universität, 80336 Munich, Germany.
authors.forename: Frank D
authors.initials: FD
authors.lastname: Goebel
authors.affiliation: Institute of Virology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Clinical Cooperation Group "Immune Monitoring", Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Institute of Virology, Technische Universität München, 81675 Munich, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Protzer
authors.affiliation: Department of Infectious Diseases, Medizinische Poliklinik, Ludwig Maximilians Universität, 80336 Munich, Germany.
authors.forename: Rika
authors.initials: R
authors.lastname: Draenert
authors.affiliation: Division of Infectious and Tropical Diseases, Hospital of Lodi, 26866 Lodi, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Tinelli
authors.affiliation: AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.|Vita-Salute San Raffaele University, School of Medicine, 20132, Milano, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Poli
authors.affiliation: Institute of Virology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Clinical Cooperation Group "Immune Monitoring", Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Erfle
authors.affiliation: Human Virology Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Malnati
authors.affiliation: Institute of Virology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Clinical Cooperation Group "Immune Monitoring", Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cosma