title: Comparison of human immunodeficiency virus (HIV)-specific T-cell responses in HIV-1- and HIV-2-infected individuals in Senegal.
abstract: Human immunodeficiency virus type 2 (HIV-2) infection is typically less virulent than HIV-1 infection, which may permit the host to mount more effective, sustained T-cell immunity. We investigated antiviral gamma interferon-secreting T-cell responses by an ex vivo Elispot assay in 68 HIV-1- and 55 HIV-2-infected Senegalese patients to determine if differences relate to more efficient HIV-2 control. Homologous HIV-specific T cells were detected in similar frequencies (79% versus 76%, P = 0.7) and magnitude (3.12 versus 3.08 log(10) spot-forming cells/10(6) peripheral blood mononuclear cells) in HIV-1 and HIV-2 infection, respectively. Gag-specific responses predominated in both groups (>/=64%), and significantly higher Nef-specific responses occurred in HIV-1-infected (54%) than HIV-2-infected patients (22%) (P < 0.001). Heterologous responses were more frequent in HIV-1 than in HIV-2 infection (46% versus 27%, P = 0.04), but the mean magnitude was similar. Total frequencies of HIV-specific responses in both groups did not correlate with plasma viral load and CD4(+) T-cell count in multivariate regression analyses. However, the magnitude of HIV-2 Gag-specific responses was significantly associated with lower plasma viremia in HIV-1-infected patients (P = 0.04). CD4(+) T-helper responses, primarily recognizing HIV-2 Gag, were detected in 48% of HIV-2-infected compared to only 8% of HIV-1-infected patients. These findings indicate that improved control of HIV-2 infection may relate to the contribution of T-helper cell responses. By contrast, the superior control of HIV-1 replication associated with HIV-2 Gag responses suggests that these may represent cross-reactive, higher-avidity T cells targeting epitopes within Gag regions of functional importance in HIV replication.
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: N N
authors.initials: NN
authors.lastname: Zheng
authors.forename: N B
authors.initials: NB
authors.lastname: Kiviat
authors.forename: P S
authors.initials: PS
authors.lastname: Sow
authors.forename: S E
authors.initials: SE
authors.lastname: Hawes
authors.forename: A
authors.initials: A
authors.lastname: Wilson
authors.forename: H
authors.initials: H
authors.lastname: Diallo-Agne
authors.forename: C W
authors.initials: CW
authors.lastname: Critchlow
authors.forename: G S
authors.initials: GS
authors.lastname: Gottlieb
authors.forename: L
authors.initials: L
authors.lastname: Musey
authors.forename: M J
authors.initials: MJ
authors.lastname: McElrath
mesh_terms: D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012675:Senegal; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015683:Gene Products, gag; D015693:Gene Products, nef; D012367:RNA, Viral; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma