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The gene for a T lymphocyte triggering factor from African trypanosomes.

Vaidya T, Bakhiet M, Hill KL, Olsson T, Kristensson K, Donelson JE - J. Exp. Med. (1997)

Bottom Line: Here, we isolate the gene for TLTF and demonstrate that the recombinant version of TLTF specifically induces CD8(+), but not CD4(+), T cells to secrete IFN-gamma.Studies with TLTF fused to the green fluorescent protein show that TLTF is localized to small vesicles that are found primarily at or near the flagellar pocket, the site of secretion in trypanosomes.TLTF is likely to be only the first example of a class of proteins that we designate as trypanokines, i.e., factors secreted by trypanosomes that modulate the cytokine network of the host immune system for the benefit of the parasite.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Iowa, and the Howard Hughes Medical Institute, Iowa City, Iowa 52242, USA.

ABSTRACT
An early and essential event in the protective immune response against most viruses and protozoa is the production of interferon-gamma (IFN-gamma). In contrast, during infection with African trypanosomes, protozoan parasites that cause human sleeping sickness, the increased levels of IFN-gamma do not correlate with a protective response. We showed previously that African trypanosomes express a protein called T lymphocyte triggering factor (TLTF), which triggers CD8(+) T lymphocytes to proliferate and to secrete IFN-gamma. Here, we isolate the gene for TLTF and demonstrate that the recombinant version of TLTF specifically induces CD8(+), but not CD4(+), T cells to secrete IFN-gamma. Studies with TLTF fused to the green fluorescent protein show that TLTF is localized to small vesicles that are found primarily at or near the flagellar pocket, the site of secretion in trypanosomes. TLTF is likely to be only the first example of a class of proteins that we designate as trypanokines, i.e., factors secreted by trypanosomes that modulate the cytokine network of the host immune system for the benefit of the parasite.

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Monoclonal antibody MO1 directed against native TLTF inhibits the biological activity of both native TLTF and recombinant GST– TLTF. The IFN-γ assays were conducted in the absence (closed bars) or  presence (cross-hatched bars) of MO1.
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Figure 4: Monoclonal antibody MO1 directed against native TLTF inhibits the biological activity of both native TLTF and recombinant GST– TLTF. The IFN-γ assays were conducted in the absence (closed bars) or presence (cross-hatched bars) of MO1.

Mentions: Next, we examined whether antibodies that specifically recognize the native TLTF molecule can inhibit the activity of recombinant TLTF. We previously demonstrated that the monoclonal antibody MO1 reduces the ability of native TLTF to induce IFN-γ secretion from CD8+ cells (4). Fig. 4 shows the results obtained when the activity of GST–TLTF was measured in the presence of MO1. Under the conditions of the assay, the activity of native TLTF was reduced by 62% in the presence of MO1. Consistent with the interpretation that GST–TLTF is the recombinant version of this protein, a concomitant decrease of 60% in the activity of GST–TLTF occurred in the presence of MO1. In the case of the unrelated GST–OV7, the number of IFN-γ–secreting cells detected in the assay was unaffected by the presence or absence of MO1.


The gene for a T lymphocyte triggering factor from African trypanosomes.

Vaidya T, Bakhiet M, Hill KL, Olsson T, Kristensson K, Donelson JE - J. Exp. Med. (1997)

Monoclonal antibody MO1 directed against native TLTF inhibits the biological activity of both native TLTF and recombinant GST– TLTF. The IFN-γ assays were conducted in the absence (closed bars) or  presence (cross-hatched bars) of MO1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199003&req=5

Figure 4: Monoclonal antibody MO1 directed against native TLTF inhibits the biological activity of both native TLTF and recombinant GST– TLTF. The IFN-γ assays were conducted in the absence (closed bars) or presence (cross-hatched bars) of MO1.
Mentions: Next, we examined whether antibodies that specifically recognize the native TLTF molecule can inhibit the activity of recombinant TLTF. We previously demonstrated that the monoclonal antibody MO1 reduces the ability of native TLTF to induce IFN-γ secretion from CD8+ cells (4). Fig. 4 shows the results obtained when the activity of GST–TLTF was measured in the presence of MO1. Under the conditions of the assay, the activity of native TLTF was reduced by 62% in the presence of MO1. Consistent with the interpretation that GST–TLTF is the recombinant version of this protein, a concomitant decrease of 60% in the activity of GST–TLTF occurred in the presence of MO1. In the case of the unrelated GST–OV7, the number of IFN-γ–secreting cells detected in the assay was unaffected by the presence or absence of MO1.

Bottom Line: Here, we isolate the gene for TLTF and demonstrate that the recombinant version of TLTF specifically induces CD8(+), but not CD4(+), T cells to secrete IFN-gamma.Studies with TLTF fused to the green fluorescent protein show that TLTF is localized to small vesicles that are found primarily at or near the flagellar pocket, the site of secretion in trypanosomes.TLTF is likely to be only the first example of a class of proteins that we designate as trypanokines, i.e., factors secreted by trypanosomes that modulate the cytokine network of the host immune system for the benefit of the parasite.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Iowa, and the Howard Hughes Medical Institute, Iowa City, Iowa 52242, USA.

ABSTRACT
An early and essential event in the protective immune response against most viruses and protozoa is the production of interferon-gamma (IFN-gamma). In contrast, during infection with African trypanosomes, protozoan parasites that cause human sleeping sickness, the increased levels of IFN-gamma do not correlate with a protective response. We showed previously that African trypanosomes express a protein called T lymphocyte triggering factor (TLTF), which triggers CD8(+) T lymphocytes to proliferate and to secrete IFN-gamma. Here, we isolate the gene for TLTF and demonstrate that the recombinant version of TLTF specifically induces CD8(+), but not CD4(+), T cells to secrete IFN-gamma. Studies with TLTF fused to the green fluorescent protein show that TLTF is localized to small vesicles that are found primarily at or near the flagellar pocket, the site of secretion in trypanosomes. TLTF is likely to be only the first example of a class of proteins that we designate as trypanokines, i.e., factors secreted by trypanosomes that modulate the cytokine network of the host immune system for the benefit of the parasite.

Show MeSH
Related in: MedlinePlus