Human immunodeficiency virus-specific CD8(+) T cells in human breast milk.
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.
Sabbaj
Steffanie
S
Departments of Medicine, University of Alabama at Birmingham, 35294-2170, USA.
Edwards
Bradley H
BH
Ghosh
Mrinal K
MK
Semrau
Katherine
K
Cheelo
Sanford
S
Thea
Donald M
DM
Kuhn
Louise
L
Ritter
G Douglas
GD
Mulligan
Mark J
MJ
Goepfert
Paul A
PA
Aldrovandi
Grace M
GM
D000293:Adolescent; D000595:Amino Acid Sequence; D001942:Breast Feeding; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D018604:Epitope Mapping; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000635:transmission; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D008895:Milk, Human / Q000276:immunology* / Q000821:virology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D010455:Peptides; D014764:Viral Proteins; D007371:Interferon-gamma