title: Detection of HIV type 1 gag-specific CD4(+) T cell responses in acutely infected infants.
abstract: Multiple HIV-1-specific cytokine and proliferative responses by CD4(+) T cells have not been studied in acutely infected infants. Using an intracellular cytokine staining assay, 34 untreated clade C HIV-1-infected infants (2-102 days old) were assessed for IFN-gamma, 28/34 for IL-2, and 26/34 for TNF-alpha responses to all HIV-1 proteins. Responses were detected in 29%, 36%, and 15% of infants, respectively. Twelve of the original 34 infants were then studied longitudinally for 14 months to determine the effect of viral load on IFN-gamma Gag-specific responses: seven infants were treated for 1 year, stopped treatment, and resumed when CD4% was < 20 and five infants were treated only when the CD4% was <20. Following treatment cessation, there was an immediate increase in viral load followed by an increase in the magnitude of CD4(+) Gag-specific responses. Despite this, the majority of infants (54%) had to restart treatment by 24 months of age, indicating that the immune responses were antigen driven but not associated with protection. Among untreated infants HIV-specific CD4(+) responses were detected sporadically indicating a dysfunctional immune response in the face of constant exposure to high levels of viremia.
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 4013 Durban, South Africa.
authors.forename: Danni
authors.initials: D
authors.lastname: Ramduth
authors.forename: Christina F
authors.initials: CF
authors.lastname: Thobakgale
authors.forename: Nompumelelo P
authors.initials: NP
authors.lastname: Mkhwanazi
authors.forename: Chantal
authors.initials: C
authors.lastname: De Pierres
authors.forename: Sharon
authors.initials: S
authors.lastname: Reddy
authors.forename: Mary
authors.initials: M
authors.lastname: van der Stok
authors.forename: Zenele
authors.initials: Z
authors.lastname: Mncube
authors.forename: Wendy
authors.initials: W
authors.lastname: Mphatswe
authors.forename: Natasha
authors.initials: N
authors.lastname: Blanckenberg
authors.forename: Ayanda
authors.initials: A
authors.lastname: Cengimbo
authors.forename: Andrew
authors.initials: A
authors.lastname: Prendergast
authors.forename: Gareth
authors.initials: G
authors.lastname: Tudor-Williams
authors.forename: Krista
authors.initials: K
authors.lastname: Dong
authors.forename: Prakash
authors.initials: P
authors.lastname: Jeena
authors.forename: Hoosen M
authors.initials: HM
authors.lastname: Coovadia
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Day
authors.forename: Photini
authors.initials: P
authors.lastname: Kiepiela
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008137:Longitudinal Studies; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; C083868:gag protein p1, Human immunodeficiency virus; D007371:Interferon-gamma