HIV-1 replication increases HIV-specific CD4+ T cell frequencies but limits proliferative capacity in chronically infected children
Graduate Program in Immunology/Virology; Department of Pediatrics; Program in Molecular Medicine
Adolescent; Adult; CD4-Positive T-Lymphocytes; Cell Division; Child; Child, Preschool; Chronic Disease; Cytomegalovirus; Down-Regulation; Epitopes, T-Lymphocyte; Gene Dosage; Gene Products, gag; HIV Infections; HIV-1; Humans; Infant; Interferon Type II; Lymphocyte Activation; Lymphocyte Count; Lymphopenia; Phosphoproteins; Protein Precursors; Viral Load; Viral Matrix Proteins; Virus Replication
Life Sciences | Medicine and Health Sciences
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/ml plasma HIV-1 RNA than in children with active HIV-1 replication. In children with/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/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.
DOI of Published Version
J Immunol. 2003 Jun 1;170(11):5786-92.
Journal of immunology (Baltimore, Md. : 1950)
Scott, Zachary Aaron; Beaumier, Coreen Michele; Sharkey, Mark E.; Stevenson, Mario; and Luzuriaga, Katherine, "HIV-1 replication increases HIV-specific CD4+ T cell frequencies but limits proliferative capacity in chronically infected children" (2003). Open Access Articles. 1110.