title: CD1d-restricted human natural killer T cells are highly susceptible to human immunodeficiency virus 1 infection.
abstract: Human natural killer (NK) T cells are unique T lymphocytes that express an invariant T cell receptor (TCR) Valpha24-Vbeta11 and have been implicated to play a role in various diseases. A subset of NKT cells express CD4 and hence are potential targets for human immunodeficiency virus (HIV)-1 infection. We demonstrate that both resting and activated human Valpha24(+) T cells express high levels of the HIV-1 coreceptors CCR5 and Bonzo (CXCR6), but low levels of CCR7, as compared with conventional T cells. Remarkably NKT cells activated with alpha-galactosylceramide (alpha-GalCer)-pulsed dendritic cells were profoundly more susceptible to infection with R5-tropic, but not X4-tropic, strains of HIV-1, compared with conventional CD4(+) T cells. Furthermore, resting CD4(+) NKT cells were also more susceptible to infection. After initial infection, HIV-1 rapidly replicated and depleted the CD4(+) subset of NKT cells. In addition, peripheral blood NKT cells were markedly and selectively depleted in HIV-1 infected individuals. Although the mechanisms of this decline are not clear, low numbers or absence of NKT cells may affect the course of HIV-1 infection. Taken together, our findings indicate that CD4(+) NKT cells are directly targeted by HIV-1 and may have a potential role during viral transmission and spread in vivo.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University Medical School, Nashville, TN 37232, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Motsinger
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
authors.forename: Aleksandar K
authors.initials: AK
authors.lastname: Stanic
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Joyce
authors.forename: Derya
authors.initials: D
authors.lastname: Unutmaz
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D018929:Cell Culture Techniques; D003713:Dendritic Cells / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D018023:HIV Seronegativity; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; D055610:Antigens, CD1d; C515370:CCR7 protein, human; C526877:CD1D protein, human; D018950:Lipopolysaccharide Receptors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine