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HIV-1 induces cytotoxic T lymphocytes in the cervix of infected women.

Musey L, Hu Y, Eckert L, Christensen M, Karchmer T, McElrath MJ - J. Exp. Med. (1997)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, The University of Washington School of Medicine, Seattle 98195, USA.

ABSTRACT
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 > or =500 cells/microl had HIV-1-specific cervical CTL, whereas only 4/11 with counts <500 cells/microl 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.

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CD4+ cervical CTL clones from subject 708 lyse HIV1-infected cells (E/T of 5:1). HIV-1 Env-specific clones lyse HIV-1-infected  autologous and MHC class II partially mismatched (donor 738) B-LCL  but not MHC class II completely mismatched (donors RML and SCHU)  B-LCL or HIV-1-uninfected cells. The CTL clones recognize epitopes  expressed by the laboratory-adapted strain, HIV-1LAI, and two primary  HIV-1 isolates, no. 1002 and no. 1005.
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Figure 3: CD4+ cervical CTL clones from subject 708 lyse HIV1-infected cells (E/T of 5:1). HIV-1 Env-specific clones lyse HIV-1-infected autologous and MHC class II partially mismatched (donor 738) B-LCL but not MHC class II completely mismatched (donors RML and SCHU) B-LCL or HIV-1-uninfected cells. The CTL clones recognize epitopes expressed by the laboratory-adapted strain, HIV-1LAI, and two primary HIV-1 isolates, no. 1002 and no. 1005.

Mentions: To assess the ability of the gp41-specific CTL clones to recognize and lyse HIV-1-infected targets, the two clones from donor 708 were tested for cytolysis of CD4-transduced B-LCL infected with either HIV-1LAI, or one of two primary low passage HIV-1 isolates, 1002 or 1005, or the uninfected control target. The clones lysed autologous targets infected with all three HIV-1 isolates but not the uninfected control targets (Fig. 3). The clones also lysed the partially mismatched targets (donor 738) but not the completely mismatched targets (donors RML and SCHU), indicating MHC class II restriction to either DR1 or DQ1 (Fig. 3). Additional studies to specifically define the class II haplotype were not performed. These studies indicate that CD4+ CTL are present in the cervix of HIV-infected women which are capable of killing HIV-1-infected cells.


HIV-1 induces cytotoxic T lymphocytes in the cervix of infected women.

Musey L, Hu Y, Eckert L, Christensen M, Karchmer T, McElrath MJ - J. Exp. Med. (1997)

CD4+ cervical CTL clones from subject 708 lyse HIV1-infected cells (E/T of 5:1). HIV-1 Env-specific clones lyse HIV-1-infected  autologous and MHC class II partially mismatched (donor 738) B-LCL  but not MHC class II completely mismatched (donors RML and SCHU)  B-LCL or HIV-1-uninfected cells. The CTL clones recognize epitopes  expressed by the laboratory-adapted strain, HIV-1LAI, and two primary  HIV-1 isolates, no. 1002 and no. 1005.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196121&req=5

Figure 3: CD4+ cervical CTL clones from subject 708 lyse HIV1-infected cells (E/T of 5:1). HIV-1 Env-specific clones lyse HIV-1-infected autologous and MHC class II partially mismatched (donor 738) B-LCL but not MHC class II completely mismatched (donors RML and SCHU) B-LCL or HIV-1-uninfected cells. The CTL clones recognize epitopes expressed by the laboratory-adapted strain, HIV-1LAI, and two primary HIV-1 isolates, no. 1002 and no. 1005.
Mentions: To assess the ability of the gp41-specific CTL clones to recognize and lyse HIV-1-infected targets, the two clones from donor 708 were tested for cytolysis of CD4-transduced B-LCL infected with either HIV-1LAI, or one of two primary low passage HIV-1 isolates, 1002 or 1005, or the uninfected control target. The clones lysed autologous targets infected with all three HIV-1 isolates but not the uninfected control targets (Fig. 3). The clones also lysed the partially mismatched targets (donor 738) but not the completely mismatched targets (donors RML and SCHU), indicating MHC class II restriction to either DR1 or DQ1 (Fig. 3). Additional studies to specifically define the class II haplotype were not performed. These studies indicate that CD4+ CTL are present in the cervix of HIV-infected women which are capable of killing HIV-1-infected cells.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, The University of Washington School of Medicine, Seattle 98195, USA.

ABSTRACT
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 > or =500 cells/microl had HIV-1-specific cervical CTL, whereas only 4/11 with counts <500 cells/microl 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.

Show MeSH
Related in: MedlinePlus