title: Broad, intense anti-human immunodeficiency virus (HIV) ex vivo CD8(+) responses in HIV type 1-infected patients: comparison with anti-Epstein-Barr virus responses and changes during antiretroviral therapy.
abstract: The ex vivo antiviral CD8(+) repertoires of 34 human immunodeficiency virus (HIV)-seropositive patients with various CD4(+) T-cell counts and virus loads were analyzed by gamma interferon enzyme-linked immunospot assay, using peptides derived from HIV type 1 and Epstein-Barr virus (EBV). Most patients recognized many HIV peptides, with markedly high frequencies, in association with all the HLA class I molecules tested. We found no correlation between the intensity of anti-HIV CD8(+) responses and the CD4(+) counts or virus load. In contrast, the polyclonality of anti-HIV CD8(+) responses was positively correlated with the CD4(+) counts. The anti-EBV responses were significantly less intense than the anti-HIV responses and were positively correlated with the CD4(+) counts. Longitudinal follow-up of several patients revealed the remarkable stability of the anti-HIV and anti-EBV CD8(+) responses in two patients with stable CD4(+) counts, while both antiviral responses decreased in two patients with obvious progression toward disease. Last, highly active antiretroviral therapy induced marked decreases in the number of anti-HIV CD8(+) T cells, while the anti-EBV responses increased. These findings emphasize the magnitude of the ex vivo HIV-specific CD8(+) responses at all stages of HIV infection and suggest that the CD8(+) hyperlymphocytosis commonly observed in HIV infection is driven mainly by virus replication, through intense, continuous activation of HIV-specific CD8(+) T cells until ultimate progression toward disease. Nevertheless, highly polyclonal anti-HIV CD8(+) responses may be associated with a better clinical status. Our data also suggest that a decrease of anti-EBV CD8(+) responses may occur with depletion of CD4(+) T cells, but this could be restored by highly active antiretroviral treatment.
authors.affiliation: Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, Unité 445, Institut Cochin de Génétique Moléculaire, Université René Descartes, Paris 75014, France. dalod@icgm.cochin.inserm.fr
authors.forename: M
authors.initials: M
authors.lastname: Dalod
authors.forename: M
authors.initials: M
authors.lastname: Dupuis
authors.forename: J C
authors.initials: JC
authors.lastname: Deschemin
authors.forename: D
authors.initials: D
authors.lastname: Sicard
authors.forename: D
authors.initials: D
authors.lastname: Salmon
authors.forename: J F
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: A
authors.initials: A
authors.lastname: Venet
authors.forename: M
authors.initials: M
authors.lastname: Sinet
authors.forename: J G
authors.initials: JG
authors.lastname: Guillet
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D006679:HIV Seropositivity / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D012189:Retrospective Studies; D014412:Tumor Virus Infections / Q000276:immunology*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D007371:Interferon-gamma