title: Human immunodeficiency virus-specific CD8+ T-cell activity is detectable from birth in the majority of in utero-infected infants.
abstract: Human immunodeficiency virus (HIV)-infected infants in sub-Saharan Africa typically progress to AIDS or death by 2 years of life in the absence of antiretroviral therapy. This rapid progression to HIV disease has been related to immaturity of the adaptive immune response in infants. We screened 740 infants born to HIV-infected mothers and tracked development and specificity of HIV-specific CD8+ T-cell responses in 63 HIV-infected infants identified using gamma interferon enzyme-linked immunospot assays and intracellular cytokine staining. Forty-four in utero-infected and 19 intrapartum-infected infants were compared to 45 chronically infected children >2 years of age. Seventy percent (14 of 20) in utero-infected infants tested within the first week of life demonstrated HIV-specific CD8+ T-cell responses. Gag, Pol, and Nef were the principally targeted regions in chronic pediatric infection. However, Env dominated the overall response in one-third (12/36) of the acutely infected infants, compared to only 2/45 (4%) of chronically infected children (P = 0.00083). Gag-specific CD4+ T-cell responses were minimal to undetectable in the first 6 months of pediatric infection. These data indicate that failure to control HIV replication in in utero-infected infants is not due to an inability to induce responses but instead suggest secondary failure of adaptive immunity in containing this infection. Moreover, the detection of virus-specific CD8+ T-cell responses in the first days of life in most in utero-infected infants is encouraging for HIV vaccine interventions in infants.
authors: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa. Thobakgalec@ukzn.ac.za
authors: Christina F
authors: CF
authors: Thobakgale
authors: Dhanwanthie
authors: D
authors: Ramduth
authors: Sharon
authors: S
authors: Reddy
authors: Nompumelelo
authors: N
authors: Mkhwanazi
authors: Chantal
authors: C
authors: de Pierres
authors: Eshia
authors: E
authors: Moodley
authors: Wendy
authors: W
authors: Mphatswe
authors: Natasha
authors: N
authors: Blanckenberg
authors: Ayanda
authors: A
authors: Cengimbo
authors: Andrew
authors: A
authors: Prendergast
authors: Gareth
authors: G
authors: Tudor-Williams
authors: Krista
authors: K
authors: Dong
authors: Prakash
authors: P
authors: Jeena
authors: Gupreet
authors: G
authors: Kindra
authors: Raziya
authors: R
authors: Bobat
authors: Hoosen
authors: H
authors: Coovadia
authors: Photini
authors: P
authors: Kiepiela
authors: Bruce D
authors: BD
authors: Walker
authors: Philip J R
authors: PJ
authors: Goulder
mesh_terms: D017954:Africa South of the Sahara; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000151:congenital* / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007372:Interferons / Q000096:biosynthesis; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus; D007372:Interferons