Significant NK cell activation associated with decreased cytolytic function in peripheral blood of HIV-1-infected patients.
One of the hallmarks of HIV-1 infection is represented by the finding of massive T cell activation in peripheral blood lymphocytes of infected patients. An impairment of NK cell function during HIV-1 infection is also detected, and is associated with decreased expression of natural cytotoxicity receptors (NCR). In this study we tried to determine whether also NK cells are affected by relevant activation and whether this could be associated with decreased NK cell function. In 18 viremic HIV-1-infected patients, freshly drawn purified peripheral NK cells displayed significant levels of activation with an incomplete pattern (HLA-DR(+)CD69(+)CD25(-)NKp44(-)). Activated (HLA-DR(+)CD69(+)) peripheral NK cells expressed an NCR(dull) phenotype as determined by cytofluorometric analysis in all the patients, and did not derive from a homogeneous/oligoclonal expansion in vivo as analyzed by expression of HLA-specific inhibitory NK cell receptors. As determined by cytotoxicity assays, activated NK cells showed a decreased cytolytic function in HIV-1-infected patients. Thus, the decrease in NK cell function observed during HIV-1 infection is associated not only with decreased NCR expression, but also with significant and incomplete NK cell activation in vivo. These results suggest a consistent continuous involvement of the innate immune response in the failure to control viral replication.
Fogli
Manuela
M
Dipartimanto di Medicina Interna, Università degli studi di Genova, Largo B. Benzi 10, I-16132 Genoa, Italy.
Costa
Paola
P
Murdaca
Giuseppe
G
Setti
Maurizio
M
Mingari
Maria Cristina
MC
Moretta
Lorenzo
L
Moretta
Alessandro
A
De Maria
Andrea
A
D015415:Biomarkers; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011971:Receptors, Immunologic / Q000276:immunology
D015415:Biomarkers; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; C112260:NCR1 protein, human; C112837:NCR2 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D052899:Pore Forming Cytotoxic Proteins; D011971:Receptors, Immunologic; D054353:Perforin