title: Short communication: CD8(+) T cell polyfunctionality profiles in progressive and nonprogressive pediatric HIV type 1 infection.
abstract: Pediatric HIV-1 infection is characterized by rapid disease progression and without antiretroviral therapy (ART), more than 50% of infected children die by the age of 2 years. However, a small subset of infected children progresses slowly to disease in the absence of ART. This study aimed to identify functional characteristics of HIV-1-specific T cell responses that distinguish children with rapid and slow disease progression. Fifteen perinatally HIV-infected children (eight rapid and seven slow progressors) were longitudinally studied to monitor T cell polyfunctionality. HIV-1-specific interferon (IFN)-γ(+) CD8(+) T cell responses gradually increased over time but did not differ between slow and rapid progressors. However, polyfunctional HIV-1-specific CD8(+) T cell responses, as assessed by the expression of four functions (IFN-γ, CD107a, TNF-α, MIP-1β), were higher in slow compared to rapid progressors (p=0.05) early in infection, and was associated with slower subsequent disease progression. These data suggest that the quality of the HIV-specific CD8(+) T cell response is associated with the control of disease in children as has been shown in adult infection.
authors.affiliation: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Christina F
authors.initials: CF
authors.lastname: Thobakgale
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.forename: Nompumelelo
authors.initials: N
authors.lastname: Mkhwanazi
authors.forename: Zenele
authors.initials: Z
authors.lastname: Mncube
authors.forename: Lungile
authors.initials: L
authors.lastname: Maphumulo
authors.forename: Fundisiwe
authors.initials: F
authors.lastname: Chonco
authors.forename: Andrew
authors.initials: A
authors.lastname: Prendergast
authors.forename: Gareth
authors.initials: G
authors.lastname: Tudor-Williams
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Goulder
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Thumbi
authors.initials: T
authors.lastname: Ndung'u
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054407:Chemokine CCL4 / Q000096:biosynthesis; D002675:Child, Preschool; D018450:Disease Progression; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C066507:CCL4 protein, human; D054407:Chemokine CCL4; D015488:HIV Antigens; D052118:Lysosomal-Associated Membrane Protein 1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma