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Journal of Virology, August 2002, p. 7365-7373, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7365-7373.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus-Specific CD8+ T Cells in Human Breast Milk

Steffanie Sabbaj,1 Bradley H. Edwards,2 Mrinal K. Ghosh,2 Katherine Semrau,2 Sanford Cheelo,3 Donald M. Thea,4 Louise Kuhn,5 G. Douglas Ritter,1 Mark J. Mulligan,1,6 Paul A. Goepfert,1,6 and Grace M. Aldrovandi2,6*

Departments of Medicine,,1 Microbiology,6 Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama,2 Zambia Exclusive Breast-Feeding Study, Lusaka, Zambia,3 Center for International Health, Boston University, Boston, Massachusetts,4 and Gertrude H. Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York5

Received 20 February 2002/ Accepted 19 April 2002

Breast-feeding infants of human immunodeficiency virus (HIV)-infected women ingest large amounts of HIV, but most escape infection. While the factors affecting transmission risk are poorly understood, HIV-specific cytotoxic T-lymphocyte (CTL) responses play a critical role in controlling HIV levels in blood. We therefore investigated the ability of breast milk cells (BMC) from HIV-infected women from the United States and Zambia to respond to HIV-1 peptides in a gamma interferon enzyme-linked immunospot assay. All (n = 11) HIV-infected women had responses to pools of Gag peptide (range, 105 to 1,400 spot-forming cells/million; mean = 718), 8 of 11 reacted to Pol, 7 reacted to Nef, and 2 of 5 reacted to Env. Conversely, of four HIV-negative women, none responded to any of the tested HIV peptide pools. Depletion and tetramer staining studies demonstrated that CD8+ T cells mediated these responses, and a chromium-release assay showed that these BMC were capable of lysing target cells in an HIV-specific manner. These data demonstrate the presence of HIV-specific major histocompatibility complex class I-restricted CD8+ CTLs in breast milk. Their presence suggests a role in limiting transmission and provides a rationale for vaccine strategies to enhance these responses.

* Corresponding author: Mailing address: Department of Pediatrics and Microbiology, University of Alabama at Birmingham, 845 19th St. South, BBRB 559, Birmingham, AL 35294-2170. Phone: (205) 934-2456. Fax: (205) 975-2457. E-mail: gracea{at}uab.edu

Journal of Virology, August 2002, p. 7365-7373, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7365-7373.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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