Innate immunity in HIV infection: enhanced susceptibility to CD95-mediated natural killer cell death and turnover induced by HIV viremia.
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.
Kottilil
Shyam
S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA. skottilil@niaid.nih.gov
Jackson
Julia O
JO
Reitano
Kristin N
KN
O'Shea
Marie Angeline
MA
Roby
Gregg
G
Lloyd
Margaret
M
Yang
Jun
J
Hallahan
Claire W
CW
Rehm
Catherine A
CA
Arthos
James
J
Lempicki
Richard
R
Fauci
Anthony S
AS
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
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