HIV-1 replication increases HIV-specific CD4+ T cell frequencies but limits proliferative capacity in chronically infected children

J Immunol. 2003 Jun 1;170(11):5786-92. doi: 10.4049/jimmunol.170.11.5786.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Division / immunology
  • Child
  • Child, Preschool
  • Chronic Disease
  • Cytomegalovirus / immunology
  • Down-Regulation / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Gene Dosage
  • Gene Products, gag / immunology
  • HIV Infections / blood
  • HIV Infections / immunology*
  • HIV Infections / pathology
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / isolation & purification
  • Humans
  • Infant
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation
  • Lymphocyte Count
  • Lymphopenia / immunology
  • Lymphopenia / pathology
  • Lymphopenia / virology
  • Phosphoproteins / immunology
  • Protein Precursors / immunology
  • Viral Load
  • Viral Matrix Proteins / immunology
  • Virus Replication / immunology*


  • Epitopes, T-Lymphocyte
  • Gene Products, gag
  • Phosphoproteins
  • Protein Precursors
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • p55 gag precursor protein, Human immunodeficiency virus 1
  • Interferon-gamma