title: An HIV-1 envelope protein vaccine elicits a functionally complex human CD4+ T cell response that includes cytolytic T lymphocytes.
abstract: T cell responses play a critical role in host defense against viral infection. Therefore, the functional properties of HIV-1-specific human T cells induced by an experimental AIDS vaccine were analyzed in detail at the clonal level. Seronegative human volunteers were immunized with a purified recombinant form of the HIV-1 envelope glycoprotein gp160 in a phase I vaccine trial. In a subset of gp160 recipients, this vaccine was shown to elicit a virus-specific CTL response. Antibody blocking and single cell cloning experiments demonstrated that the vaccine-induced cytolytic activity was mediated by CD4+, MHC class II-restricted T cells. Because little is known about the regulation of CD4+ CTL in any system, a detailed analysis of CTL responses in vaccinees was carried out. Longitudinal and cross-sectional studies revealed that the CD4+ CTL response was regulated in a complex manner and was not clearly correlated with MHC class II genotype, Ag dose, or number of immunizations. Cloning studies were carried out to determine what fraction of the vaccine-induced T cells were cytolytic and to examine patterns of cytokine production by vaccine-induced T cells. These experiments demonstrated that, for some vaccinees, CD4+ CTL dominated the in vitro T cell response to gp160 at certain time points. The level of cytolytic activity, which was a stable property of individual clones, varied among clones over a wide and continuous range. Analysis of cytokine secretion by gp160-specific CD4+ T cell clones revealed Th0-, Th1-, and Th2-like patterns, with CD4+ CTL clones showing Th0- or T'1-like patterns. Interestingly, many Th0- and Th1-like CTL clones produced very little IL-2, a finding that may explain the complicated regulation of this response. These results illustrate the complex nature of the human T cell response to subunit vaccines consisting of purified recombinant viral proteins.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: P E
authors.initials: PE
authors.lastname: Stanhope
authors.forename: A Y
authors.initials: AY
authors.lastname: Liu
authors.forename: W
authors.initials: W
authors.lastname: Pavlat
authors.forename: P M
authors.initials: PM
authors.lastname: Pitha
authors.forename: M L
authors.initials: ML
authors.lastname: Clements
authors.forename: R F
authors.initials: RF
authors.lastname: Siliciano
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D015686:Gene Products, env / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019302:HIV Envelope Protein gp160; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D011498:Protein Precursors / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D016693:Receptors, Antigen, T-Cell, alpha-beta