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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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Related in: MedlinePlus

T lymphocytes in fresh cervical preparations and following  clonal expansion. Two-color cytofluorimetric analysis of freshly isolated  cervical mononuclear cells (A) and cervical CTL clones (B) obtained from  HIV-1-infected women: volunteer 737 (A, upper panels), volunteer 747  (A, lower panels), and volunteer 710 (B, both panels). Left-hand plots represent the two antibody isotype controls (IgG1 FITC and IgG2a PE). (A)  Middle plots demonstrate expression of CD3 (FL1) and CD16 (FL2). Surface expression of CD4 (FL1) and CD8 (FL2) are shown in A (right-hand  plots) and B (middle plots). TCRαβ (FL1) and TCRγδ (FL2) are shown in  B (right-hand plot).
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Figure 1: T lymphocytes in fresh cervical preparations and following clonal expansion. Two-color cytofluorimetric analysis of freshly isolated cervical mononuclear cells (A) and cervical CTL clones (B) obtained from HIV-1-infected women: volunteer 737 (A, upper panels), volunteer 747 (A, lower panels), and volunteer 710 (B, both panels). Left-hand plots represent the two antibody isotype controls (IgG1 FITC and IgG2a PE). (A) Middle plots demonstrate expression of CD3 (FL1) and CD16 (FL2). Surface expression of CD4 (FL1) and CD8 (FL2) are shown in A (right-hand plots) and B (middle plots). TCRαβ (FL1) and TCRγδ (FL2) are shown in B (right-hand plot).

Mentions: By cytofluorimetric analysis of fresh, filtered cytobrush specimens, CD3+ T cells commonly comprised ⩽5% of the mononuclear cell population (Fig. 1 A) but could proliferate upon antigen-specific stimulation to purified CD4+ or CD8+ T cell populations (Fig. 1 B). Of these, typically <2% were CD4+ or CD8+ T cells, as shown in Fig. 1 A in two representative donors. The CD3−CD16+ NK cells were present in variable frequencies, ranging from 0–71% (median 23%) of the five donors examined. Because the T cells were few in the initial specimen, the phenotype of the T cells isolated on the day of collection did not predict the ability to later demonstrate CD8+ or CD4+ cytolytic activity in cell lines or clones.


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)

T lymphocytes in fresh cervical preparations and following  clonal expansion. Two-color cytofluorimetric analysis of freshly isolated  cervical mononuclear cells (A) and cervical CTL clones (B) obtained from  HIV-1-infected women: volunteer 737 (A, upper panels), volunteer 747  (A, lower panels), and volunteer 710 (B, both panels). Left-hand plots represent the two antibody isotype controls (IgG1 FITC and IgG2a PE). (A)  Middle plots demonstrate expression of CD3 (FL1) and CD16 (FL2). Surface expression of CD4 (FL1) and CD8 (FL2) are shown in A (right-hand  plots) and B (middle plots). TCRαβ (FL1) and TCRγδ (FL2) are shown in  B (right-hand plot).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: T lymphocytes in fresh cervical preparations and following clonal expansion. Two-color cytofluorimetric analysis of freshly isolated cervical mononuclear cells (A) and cervical CTL clones (B) obtained from HIV-1-infected women: volunteer 737 (A, upper panels), volunteer 747 (A, lower panels), and volunteer 710 (B, both panels). Left-hand plots represent the two antibody isotype controls (IgG1 FITC and IgG2a PE). (A) Middle plots demonstrate expression of CD3 (FL1) and CD16 (FL2). Surface expression of CD4 (FL1) and CD8 (FL2) are shown in A (right-hand plots) and B (middle plots). TCRαβ (FL1) and TCRγδ (FL2) are shown in B (right-hand plot).
Mentions: By cytofluorimetric analysis of fresh, filtered cytobrush specimens, CD3+ T cells commonly comprised ⩽5% of the mononuclear cell population (Fig. 1 A) but could proliferate upon antigen-specific stimulation to purified CD4+ or CD8+ T cell populations (Fig. 1 B). Of these, typically <2% were CD4+ or CD8+ T cells, as shown in Fig. 1 A in two representative donors. The CD3−CD16+ NK cells were present in variable frequencies, ranging from 0–71% (median 23%) of the five donors examined. Because the T cells were few in the initial specimen, the phenotype of the T cells isolated on the day of collection did not predict the ability to later demonstrate CD8+ or CD4+ cytolytic activity in cell lines or clones.

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