title: Memory CD8(+) T cells elicited by HIV-1 lipopeptide vaccines display similar phenotypic profiles but differences in term of magnitude and multifunctionality compared with FLU- or EBV-specific memory T cells in humans.
abstract: Differentiation marker, multifunctionality and magnitude analyses of specific-CD8(+) memory T cells are crucial to improve development of HIV vaccines designed to generate cell-mediated immunity. Therefore, we fully characterized the HIV-specific CD8(+) T cell responses induced in volunteers vaccinated with HIV lipopeptide vaccines for phenotypic markers, tetramer staining, cytokine secretion, and cytotoxic activities. The frequency of ex vivo CD8(+) T cells elicited by lipopeptide vaccines is very rare and central-memory phenotype and functions of these cells were been shown to be important in AIDS immunity. So, we expanded them using specific peptides to compare the memory T cell responses induced in volunteers by HIV vaccines with responses to influenza (FLU) or Epstein Barr virus (EBV). By analyzing the differentiation state of IFN-γ-secreting CD8(+) T cells, we found a CCR7(-)CD45RA(-)CD28(+int)/CD28(-) profile (>85%) belonging to a subset of intermediate-differentiated effector T cells for HIV, FLU, and EBV. We then assessed the quality of the response by measuring various T cell functions. The percentage of single IFN-γ T cell producers in response to HIV was 62% of the total of secreting T cells compared with 35% for FLU and EBV, dual and triple (IFN-γ/IL-2/CD107a) T cell producers could also be detected but at lower levels (8% compared with 37%). Finally, HIV-specific T cells secreted IFN-γ and TNF-α, but not the dual combination like FLU- and EBV-specific T cells. Thus, we found that the functional profile and magnitude of expanded HIV-specific CD8(+) T precursors were more limited than those of to FLU- and EBV-specific CD8(+) T cells. These data show that CD8(+) T cells induced by these HIV vaccines have a similar differentiation profile to FLU and EBV CD8(+) T cells, but that the vaccine potency to induce multifunctional T cells needs to be increased in order to improve vaccination strategies.
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France; CNRS UMR8104, Paris, France; Univ Paris Descartes, Paris, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Figueiredo
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France; CNRS UMR8104, Paris, France; Univ Paris Descartes, Paris, France.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Charmeteau
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France; CNRS UMR8104, Paris, France; Univ Paris Descartes, Paris, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Surenaud
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Cochin, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.affiliation: Inserm CIC BT505, CIC de Vaccinologie Cochin Pasteur, Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Launay
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France; CNRS UMR8104, Paris, France; Univ Paris Descartes, Paris, France.
authors.forename: Jean-Gérard
authors.initials: JG
authors.lastname: Guillet
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France; CNRS UMR8104, Paris, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Cochin, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Hosmalin
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France; CNRS UMR8104, Paris, France; Univ Paris Descartes, Paris, France; Institut National de Santé et de Recherche Médicale, INSERM U976, Saint-Louis Hospital, Skin Research Center, 75010 Paris, France; Paris Diderot University, Sorbonne Paris Cité, Laboratory of Immunology, Dermatology & Oncology, UMR-S 976, 75010 Paris, France. Electronic address: hanne.gahery@inserm.fr.
authors.forename: Hanne
authors.initials: H
authors.lastname: Gahery
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1; D064368:Healthy Volunteers; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D007251:Influenza, Human / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D055666:Lipopeptides; D008213:Lymphocyte Activation
chemical_list: D016915:AIDS Vaccines; D055666:Lipopeptides; D007371:Interferon-gamma
keywords: CD8(+) T cells; Cytokines; Differentiation; HIV-lipopeptide vaccine; Human; Maturation