title: HIV-1 replication increases HIV-specific CD4+ T cell frequencies but limits proliferative capacity in chronically infected children.
abstract: This study investigated the relationship between HIV-1 replication and virus (HIV-1; CMV)-specific CD4(+) T cell frequency and function in HIV-1-infected children. HIV-1 gag p55-specific CD4(+) T cell IFN-gamma responses were detected in the majority of children studied. p55-specific responses were detected less commonly and at lower frequencies in children with <50 copies/ml plasma HIV-1 RNA than in children with active HIV-1 replication. In children with <50 copies/ml plasma HIV-1, p55-specific responses were detected only in children with evidence of ongoing HIV-1 replication, indicating a direct relationship between HIV-1 replication and HIV-specific CD4(+) T cell frequencies. In contrast, p55-specific proliferative responses were detected more frequently in children with <50 copies/ml plasma HIV-1. CMV-specific CD4(+) responses were more commonly detected and at higher frequencies in CMV-coinfected children with suppressed HIV-1 replication. The lack of HIV-specific CD4(+) proliferative responses, along with the preservation of CMV-specific CD4(+) responses in children with controlled HIV-1 replication, suggests that viral replication may have deleterious effects on HIV-1 and other virus-specific CD4(+) responses. Vaccination to stimulate HIV-specific CD4(+) T cell responses in these children may synergize with antiretroviral therapy to improve the long-term control of viral replication, and may perhaps allow the eventual discontinuation of antiretroviral therapy.
authors.affiliation: Graduate Program in Immunology/Virology and Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Scott
authors.forename: Coreen M
authors.initials: CM
authors.lastname: Beaumier
authors.forename: Mark
authors.initials: M
authors.lastname: Sharkey
authors.forename: Mario
authors.initials: M
authors.lastname: Stevenson
authors.forename: Katherine
authors.initials: K
authors.lastname: Luzuriaga
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002455:Cell Division / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003587:Cytomegalovirus / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D018628:Gene Dosage; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology / Q000821:virology; D010750:Phosphoproteins / Q000276:immunology; D011498:Protein Precursors / Q000276:immunology; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000276:immunology; D014779:Virus Replication / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D010750:Phosphoproteins; D011498:Protein Precursors; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D007371:Interferon-gamma