title: HIV-specific CD8+ T cell function in children with vertically acquired HIV-1 infection is critically influenced by age and the state of the CD4+ T cell compartment.
abstract: The immunology of vertical HIV transmission differs from that of adult infection in that the immune system of the infant is not fully matured, and the factors that influence the functionality of CD8(+) T cell responses against HIV in children remain largely undefined. We have investigated CD8(+) T cell responses in 65 pediatric subjects with vertically acquired HIV-1 infection. Vigorous, broad, and Ag dose-driven CD8(+) T cell responses against HIV Ags were frequently observed in children who were older than 3 years of age and maintained CD4(+) T cell counts >400 cells/ micro l. In contrast, younger age or a CD4(+) T cell count <400 cells/ micro l was associated with poor CD8(+) T cell responses and high HIV loads. Furthermore, subjects with a severely depleted and phenotypically altered CD4(+) T cell compartment had circulating Gag-specific CD8(+) T cells with impaired IFN-gamma production. When viral load was not suppressed by antiviral treatment, subjects that fell below the putative age and CD4(+) T cell count thresholds had significantly reduced CD8(+) T cell responses and significantly higher viral loads. Thus, the data suggest that fully effective HIV-specific CD8(+) T cell responses take years to develop despite an abundance of Ag in early life, and responses are further severely impaired, independent of age, in children who have a depleted or skewed CD4(+) T cell compartment. The results are discussed in relation to differences between the neonatal and adult immune systems in the ability to respond to HIV infection.
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94141, USA.
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
authors.forename: Noam M
authors.initials: NM
authors.lastname: Fast
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Jordan
authors.forename: Scott N
authors.initials: SN
authors.lastname: Furlan
authors.forename: Jason D
authors.initials: JD
authors.lastname: Barbour
authors.forename: Glenn
authors.initials: G
authors.lastname: Fennelly
authors.forename: Joanna
authors.initials: J
authors.lastname: Dobroszycki
authors.forename: Hans M L
authors.initials: HM
authors.lastname: Spiegel
authors.forename: Andrew
authors.initials: A
authors.lastname: Wiznia
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenberg
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
mesh_terms: D000293:Adolescent; D000375:Aging / Q000276:immunology*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood; D008297:Male; D019562:Viral Load
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015488:HIV Antigens; D007371:Interferon-gamma