title: CD1d-restricted natural killer T cells are potent targets for human immunodeficiency virus infection.
abstract: Invariant human natural killer T cells (NKT) express a restricted T-cell receptor (TCR) Valpha24Vbeta11 repertoire. These cells share both phenotypic and functional similarities between NK and T cells. Given the emerging role of NKT cells as critical cells in bridging the gap between innate and adaptive immunity, we examined their susceptibility to productive human immunodeficiency virus (HIV) infection by T-tropic, M-tropic, and primary isolates of HIV. We generated three human NKT cell clones (CA5, CA29, and CA31). Phenotypic characterization of these Valpha24+ Vbeta11+ clones indicated that they were predominately positive for CD4, CD161, HLA-DR, CD38, CD45RO, and CD95 expression. The NKT cell clones expressed significantly more surface CCR5 molecules/cell and lower CXCR4 molecules/cell than phytohaemagglutinin-stimulated peripheral blood mononuclear cells (PBMC). Consistent with the surface expression of CCR5 and CXCR4, the NKT clones were also selectively susceptible to HIV M-tropic, T-tropic, and primary isolate infection, as evaluated by both HIV p24 enzyme-linked immunosorbent assay and intracellular staining of HIV proteins. The amount of p24 production was dependent on the NKT clone studied and the HIV strain used. Clones CA29 and CA31 were also susceptible to HIV IIIB infection. The virions produced by these clones were able to productively infect PHA-stimulated PBMCs with the same kinetics as for primary infection of CD4+ blast. Collectively, this data demonstrates that NKT cells can be a target for productive HIV infection but with a lag in the time to peak p24 production.
authors.affiliation: Department of Immunology/Microbiology and Division of Infectious Diseases, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
authors.forename: Richardson
authors.initials: R
authors.lastname: Fleuridor
authors.forename: Brian
authors.initials: B
authors.lastname: Wilson
authors.forename: Runhua
authors.initials: R
authors.lastname: Hou
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Harold
authors.initials: H
authors.lastname: Kessler
authors.forename: Lena
authors.initials: L
authors.lastname: Al-Harthi
mesh_terms: D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D018929:Cell Culture Techniques / Q000379:methods; D002999:Clone Cells / Q000276:immunology; D004198:Disease Susceptibility; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016655:HIV Core Protein p24; D019713:Receptors, CCR5; D019718:Receptors, CXCR4