title: Deficient human immunodeficiency virus type 1-specific cytotoxic T cell responses in vertically infected children.
abstract: Cytotoxic T lymphocyte (CTL) responses to human immunodeficiency virus type 1 (HIV-1) gag proteins were studied prospectively in 17 children (12 infected) born of mothers with HIV-1 seropositivity and in five pediatric patients with hemophilia infected by transfusion of HIV-1-contaminated factor VIII concentrate. B lymphoblastoid cells infected with vaccinia virus vectors expressing HIV-1 gag gene products were combined with autologous peripheral blood mononuclear cells to detect circulating CTLs. Effector cells were defined by monoclonal antibody-mediated, complement-dependent cytolysis. Circulating HIV-1 gag-specific cytotoxic responses were detectable in 4 of 5 HIV-1-infected pediatric hemophilic patients, and were similar in magnitude to those previously described in adults. In contrast, circulating HIV-1 gag-specific cytolysis was detectible in only 3 of 12 vertically infected children. Depletion data revealed that the majority of detectible gag-specific cytolysis was CD8 T cell-mediated. No apparent relationships between CD4 T cell counts, CD8 T cells counts, or serum p24 antigen levels and CTL responses were seen. Deficient CTL development may, in part, explain the more rapid onset of symptomatic disease following vertical HIV infection.
authors.affiliation: Department of Pediatrics, University of Massachusetts Medical School, Worcester 01605.
authors.forename: K
authors.initials: K
authors.lastname: Luzuriaga
authors.forename: R A
authors.initials: RA
authors.lastname: Koup
authors.forename: C A
authors.initials: CA
authors.lastname: Pikora
authors.forename: D B
authors.initials: DB
authors.lastname: Brettler
authors.forename: J L
authors.initials: JL
authors.lastname: Sullivan
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000635:transmission; D000293:Adolescent; D015703:Antigens, CD / Q000097:blood; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood; D015704:CD4 Antigens / Q000097:blood; D016827:CD8 Antigens; D002648:Child; D002675:Child, Preschool; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D015683:Gene Products, gag / Q000097:blood / Q000276:immunology; D015488:HIV Antigens / Q000097:blood; D016655:HIV Core Protein p24; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000635:transmission; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006467:Hemophilia A / Q000150:complications / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007223:Infant; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000097:blood; D014776:Virus Cultivation
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D014758:Viral Core Proteins