title: Downregulation of CD94/NKG2A inhibitory receptors on CD8+ T cells in HIV infection is more pronounced in subjects with detected viral load than in their aviraemic counterparts.
abstract: The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated CD8+ T lymphocytes. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In this study, CD94/NKG2A receptor expression on CD8+ T lymphocytes and NK cells was assessed in 46 HIV-1-infected patients (24 viraemic, 22 aviraemic) and 10 healthy volunteers. The percentage of CD8+ T lymphocytes expressing the CD94/NKG2A inhibitory heterodimer was very significantly decreased in HIV-1-infected patients in comparison with non-infected controls. Within the HIV infected patients, the proportion of CD8+ T lymphocytes and NK cells expressing CD94/NKG2A was higher in subjects with undetectable viral loads in comparison with their viraemic counterparts. No significant difference was detected in the proportion of CD8+ T lymphocytes expressing the activatory CD94/NKG2C heterodimer between the HIV-1 infected patients and the healthy donors, nor between the vireamic and avireamic HIV-1 infected patients. In conclusion, chronic stimulation with HIV antigens in viraemic patients leads to a decreased rather than increased CD94/NKG2A expression on CD8+ T lymphocytes and NK cells.
authors.affiliation: University of Liège, Laboratory of Immunology and Infectious Diseases, GIGA-R, Liège, Belgium. mzeddou@ulg.ac.be
authors.forename: Mustapha
authors.initials: M
authors.lastname: Zeddou
authors.forename: Souad
authors.initials: S
authors.lastname: Rahmouni
authors.forename: Arnaud
authors.initials: A
authors.lastname: Vandamme
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jacobs
authors.forename: Frédéric
authors.initials: F
authors.lastname: Frippiat
authors.forename: Philippe
authors.initials: P
authors.lastname: Leonard
authors.forename: Nicole
authors.initials: N
authors.lastname: Schaaf-Lafontaine
authors.forename: Dolores
authors.initials: D
authors.lastname: Vaira
authors.forename: Jacques
authors.initials: J
authors.lastname: Boniver
authors.forename: Michel
authors.initials: M
authors.lastname: Moutschen
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002908:Chronic Disease; D015536:Down-Regulation; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D019562:Viral Load
chemical_list: C527054:KLRC1 protein, human; C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell