HLA-E up-regulation induced by HIV infection may directly contribute to CD94-mediated impairment of NK cells.
Alterations in NK cell numbers and function have been repeatedly shown during HIV infection. In this study, NK cell number and MHC class I expression on CD4+ T cells were studied in HIV patients at different stages of disease progression. An increased expression of HLA-E was seen on CD4+ T cells. In parallel, a reduced number of CD94+ NK cells was observed in advanced disease stages. Moreover, a decline in CD94 expression on NK cells was observed at the HIV replication peak in patients undergoing antiretroviral treatment interruption, suggesting a role of viral replication on NK cells alterations. In vitro HIV infection induced a rapid down-regulation of HLA-A,B,C expression, paralleled by an increased expression of HLA-E surface molecules, the formal ligands of CD94 NK receptors. HIV-infected HLA-E expressing cells were able to inhibit NK cell cytotoxicity through HLA-E expression, since cytotoxicity was restored by antibody masking experiments. These data indicate that the CD94/HLA-E interaction may contribute to NK cell dysfunction in HIV infection, suggesting a role of HIV replication in this process.
Martini
F
F
National Institute for Infectious Diseases (I.N.M.I.), Lazzaro Spallanzani, I.R.C.C.S., Rome, Italy. martini@inmi.it
Agrati
C
C
D'Offizi
G
G
Poccia
F
F
D015703:Antigens, CD / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003602:Cytotoxicity, Immunologic; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006680:HLA Antigens / Q000096:biosynthesis* / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology*; D018655:Lymphocyte Count; D051920:NK Cell Lectin-Like Receptor Subfamily D; D015854:Up-Regulation; D014779:Virus Replication / Q000276:immunology; D000097625:HLA-E Antigens
D015703:Antigens, CD; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D051920:NK Cell Lectin-Like Receptor Subfamily D; D000097625:HLA-E Antigens; C497869:KLRD1 protein, human