Could natural killer cells compensate for impaired CD4+ T-cell responses to CMV in HIV patients responding to antiretroviral therapy?
We evaluated NK cell subsets and functions in previously immunodeficient HIV patients responding to ART. Cytokine receptor mRNA was quantitated in purified CD56+ cells. Data were correlated with CD4+ T-cell counts and IFNgamma responses to CMV. NK cell IFNgamma responses to K562 cells and proportions of CD56lo NK cells were correlated in patients (p < 0.001) and both were lower than in controls (p < 0.001 and p = 0.008, respectively), so all patients had poor NK cell function. Proportions of CD56hi NK cells correlated inversely with current CD4+ T-cell counts (p = 0.006) and perforin expression in CD56hi NK cells was higher in patients than controls (p < 0.05). Hence increased proportions and cytolytic function of CD56hi NK cells may partially compensate for CD4+ T-cell deficiency. NK cell IFNgamma responses correlated inversely with expression of IL-10 and IL-12 receptor mRNA. Expression of these transcripts is reduced by exposure to the cytokines, which may reflect immune activation in immunodeficient patients.
Tan
Dino Bee Aik
DB
School of Pathology and Laboratory Medicine, University of Western Australia, Australia.
Fernandez
Sonia
S
French
Martyn
M
Price
Patricia
P
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019002:CD56 Antigen / Q000276:immunology; D003587:Cytomegalovirus / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053707:Receptors, Interleukin-12 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000998:Antiviral Agents; D019002:CD56 Antigen; D012333:RNA, Messenger; D053701:Receptors, Interleukin-10; D053707:Receptors, Interleukin-12; D054353:Perforin; D007371:Interferon-gamma