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Journal of Virology, December 2007, p. 12775-12784, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.00624-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus-Specific CD8+ T-Cell Activity Is Detectable from Birth in the Majority of In Utero-Infected Infants{triangledown}

Christina F. Thobakgale,1* Dhanwanthie Ramduth,1 Sharon Reddy,1 Nompumelelo Mkhwanazi,1 Chantal de Pierres,1 Eshia Moodley,1 Wendy Mphatswe,1 Natasha Blanckenberg,1 Ayanda Cengimbo,1 Andrew Prendergast,2 Gareth Tudor-Williams,3 Krista Dong,4 Prakash Jeena,1 Gupreet Kindra,1 Raziya Bobat,1 Hoosen Coovadia,1 Photini Kiepiela,1 Bruce D. Walker,1,4,5 and Philip J. R. Goulder1,2,4

HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa,1 Department of Paediatrics, Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Rd., Oxford OX1 3SY, United Kingdom,2 Department of Paediatrics, Imperial College of London, London, United Kingdom,3 Partners AIDS Research Center, Massachusetts General Hospital, 13th St., Bldg. 149, Charlestown, Boston, Massachusetts 02129,4 Howard Hughes Medical Institute, Chevy Chase, Maryland5

Received 23 March 2007/ Accepted 28 August 2007

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.

* Corresponding author. Mailing address: HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa. Phone: 27 31 260 4608. Fax: 27 31 260 4036. E-mail: Thobakgalec{at}ukzn.ac.za

{triangledown} Published ahead of print on 19 September 2007.

Journal of Virology, December 2007, p. 12775-12784, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.00624-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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