title: 2B4 expression on natural killer cells increases in HIV-1 infected patients followed prospectively during highly active antiretroviral therapy.
abstract: Human immunodeficiency virus (HIV)-1 infection influences natural killer (NK) cell expression of inhibitory NK receptors and activating natural cytotoxicity receptors. It is unknown whether expression of the co-stimulatory NK cell receptor 2B4 (CD244) on NK cells and CD3+ CD8+ cells are affected by highly active antiretroviral therapy (HAART), low-level viraemia, proviral-DNA or immune activation in HIV-1 infected patients. A total of 101 HAART-treated HIV-1 infected patients with < or = 200 HIV-RNA copies/ml were followed prospectively for 24 months. HIV-RNA was investigated 3-monthly and 2B4 expression on CD3- CD16+ NK cells and CD3+ CD8+ cells, proviral-DNA and plasma soluble tumour necrosis factor receptor (sTNFr)-II were investigated 6-monthly. For comparison, 2B4 expression was investigated in 20 healthy individuals. The concentration of 2B4+ NK cells was initially reduced in HIV-1 infected patients (P < 0.001) but increased to a normal level during the 24 months' follow-up. The concentration of CD3+ CD8+ 2B4+ cells in HIV-1 infected patients was normal and did not change during follow-up. The relative fluorescence intensity (RFI) of 2B4 increased on both NK cells and CD3+ CD8+ cells during follow-up (both P < 0.001). Higher levels of proviral-DNA carrying cells and plasma sTNFrII were associated with reductions in the concentration of 2B4+ NK cells (all P < 0.05). HIV-RNA had no effect on 2B4 expression on NK cells or CD3+ CD8+ cells. These findings demonstrate that the concentration of 2B4+ NK cells normalizes during long-term HAART in HIV-1 infected patients. The finding that proviral-DNA and sTNFrII were associated negatively with the concentration of 2B4+ NK cells suggests that immune activation in HIV-1 infected patients receiving HAART influences the target cell recognition by NK cells.
authors.affiliation: Department of Infectious Diseases, Rishospitalet, Copenhagen, Denmark. sro@dadlnet.dk
authors.forename: S R
authors.initials: SR
authors.lastname: Ostrowski
authors.forename: H
authors.initials: H
authors.lastname: Ullum
authors.forename: B K
authors.initials: BK
authors.lastname: Pedersen
authors.forename: J
authors.initials: J
authors.lastname: Gerstoft
authors.forename: T L
authors.initials: TL
authors.lastname: Katzenstein
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D015233:Models, Statistical; D011446:Prospective Studies; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D000071176:Signaling Lymphocytic Activation Molecule Family; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; C084093:CD244 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D018124:Receptors, Tumor Necrosis Factor; D000071176:Signaling Lymphocytic Activation Molecule Family