title: Innate immunity in HIV infection: enhanced susceptibility to CD95-mediated natural killer cell death and turnover induced by HIV viremia.
abstract: In the present study, we performed DNA microarray analyses and phenotypic and functional analyses in an effort to elucidate the mechanisms by which ongoing HIV replication affects the physiologic function of natural killer (NK) cells. Functional assays confirmed an increased propensity of NK cells from HIV-infected viremic individuals to undergo Fas-mediated apoptosis but not CD16- or NKG2D-mediated apoptosis. Serum levels of sFasL and expression of Ki67 on NK cells were markedly elevated in HIV-infected viremic individuals when compared with those of HIV-infected aviremic and HIV-seronegative individuals. Our data demonstrate that ongoing HIV replication results in profound NK-cell abnormalities that are likely to be attributable to the effects of virus-induced immune activation. Of note is an increased susceptibility to cell death mediated by CD95-sFasL interactions. In addition, these NK cells, particularly the CD56(dim) CD16(bright) subset, undergo enhanced cell turnover in vivo, as demonstrated by intracellular Ki67 expression.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA. skottilil@niaid.nih.gov
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: Julia O
authors.initials: JO
authors.lastname: Jackson
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Reitano
authors.forename: Marie Angeline
authors.initials: MA
authors.lastname: O'Shea
authors.forename: Gregg
authors.initials: G
authors.lastname: Roby
authors.forename: Margaret
authors.initials: M
authors.lastname: Lloyd
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Claire W
authors.initials: CW
authors.lastname: Hallahan
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Rehm
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.forename: Richard
authors.initials: R
authors.lastname: Lempicki
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000097:blood; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D040081:Protein Array Analysis; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D014766:Viremia; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; C527085:KLRK1 protein, human; D019394:Ki-67 Antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D019014:fas Receptor