© The Rockefeller University Press, 0022-1007/1997/1/293/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 2, January 20, 1997 293-304
HIV-1 Induces Cytotoxic T Lymphocytes in the Cervix of Infected Women
Luwy Musey,
Yuxiang Hu,
Linda Eckert,
Michael Christensen,
Tobi Karchmer, and
M. Juliana McElrath
From the Departments of Medicine and Obstetrics and Gynecology, The University of Washington School of Medicine, Seattle, Washington 98195
Although T lymphocytes are present in the genital mucosa, their function in sexually transmitted diseases is unproven. To determine if cervical T cells mediate HIV-specific cytolysis, mononuclear cells in cytobrush specimens from HIV-1-infected women were stimulated in vitro with antigen. Resultant cell lines lysed autologous targets expressing HIV-1 proteins in 12/19 (63%) subjects, and these responses were detected intermittently on repeated visits. All 8 subjects with blood CD4+ counts
500 cells/µl had HIV-1-specific cervical CTL, whereas only 4/11 with counts <500 cells/µl had detectable responses (P = 0.008). Class II MHC– restricted CD4+ CTL clones lysed targets expressing Env gp41 or infected with HIV-1. Class I MHC-restricted CD8+ clones recognized HIV-1 Gag- or Pol-expressing targets, and the epitopes were mapped to within 9–20 amino acids. Comparisons of intra-individual cervical and blood CTL specificities indicate that epitopes recognized by CTL in the cervix were commonly recognized in the blood. These studies provide the first definitive evidence for an MHC-restricted effector function in human cervical lymphocytes.
Address correspondence to Dr. M. Juliana McElrath at the Fred Hutchinson Cancer Research Center, Clinical Research Division, M-115, 1124 Columbia St., Seattle, WA 98104.
This investigation was supported in part by National Institutes of Health grants AI 35605, AI 27757, and AI 07140. L. Musey was a recipient of a IARTP Fellowship (D43TW00007).
1 Abbreviations used in this paper: aa, amino acids; rVV, recombinant vaccinia vectors.

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-
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[Full Text]
-
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-
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-
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-
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(2000). Induction of Mucosal Homing Virus-Specific CD8+ T Lymphocytes by Attenuated Simian Immunodeficiency Virus. J. Virol.
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-
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(2000). HIV-1-Specific Mucosal CD8+ Lymphocyte Responses in the Cervix of HIV-1-Resistant Prostitutes in Nairobi. J. Immunol.
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[Abstract]
[Full Text]
-
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[Abstract]
[Full Text]
-
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(1999). Detection of Simian Immunodeficiency Virus Gag-Specific CD8+ T Lymphocytes in Semen of Chronically Infected Rhesus Monkeys by Cell Staining with a Tetrameric Major Histocompatibility Complex Class I-Peptide Complex. J. Virol.
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[Abstract]
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-
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(1999). Intranasal Immunization with Plasmid DNA-Lipid Complexes Elicits Mucosal Immunity in the Female Genital and Rectal Tracts. J. Immunol.
162: 254-262
[Abstract]
[Full Text]
-
Kent, S. J., Zhao, A., Best, S. J., Chandler, J. D., Boyle, D. B., Ramshaw, I. A.
(1998). Enhanced T-Cell Immunogenicity and Protective Efficacy of a Human Immunodeficiency Virus Type 1 Vaccine Regimen Consisting of Consecutive Priming with DNA and Boosting with Recombinant Fowlpox Virus. J. Virol.
72: 10180-10188
[Abstract]
[Full Text]
-
Belyakov, I. M., Derby, M. A., Ahlers, J. D., Kelsall, B. L., Earl, P., Moss, B., Strober, W., Berzofsky, J. A.
(1998). Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge. Proc. Natl. Acad. Sci. USA
95: 1709-1714
[Abstract]
[Full Text]
-
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(1997). Cytotoxic-T-Cell Responses, Viral Load, and Disease Progression in Early Human Immunodeficiency Virus Type 1 Infection. NEJM
337: 1267-1274
[Abstract]
[Full Text]