The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/8/433/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 3, August 4, 1997 433-438

Articles

The Gene for a T Lymphocyte Triggering Factor from African Trypanosomes

Tushar Vaidya*, Moiz Bakhiet{ddagger},§, Kent L. Hill*, Tomas Olsson{ddagger}, Krister Kristensson||, and John E. Donelson*

From the * Department of Biochemistry, University of Iowa, and the Howard Hughes Medical Institute, Iowa City, Iowa 52242; {ddagger} Department of Medicine, Unit for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden; § Division of Neurology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden; and the || Department of Neuroscience (Division of Neurodegenerative Disease Research), Karolinska Institute, Stockholm, Sweden

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.

Address correspondence to John E. Donelson, Department of Biochemistry, University of Iowa, Iowa City, IA 52242. Phone: 319-335-7889; FAX: 319-335-6764. The current address for Tushar Vaidya is Center for Cellular and Molecular Biology, Uppal Rd., Habshiguda, Hyderbad, India 500007.

This research was funded in part by a grant from the United Nations Development Program/World Bank/ World Health Organization Special Program for Research and Training in Tropical Disease to M. Bakhiet, T. Olsson, and K. Kristensson.

1 Abbreviations used in this paper: ADF, adult T cell leukemia-derived factor; GFP, green fluorescent protein; GST, glutathione-S-transferase; IGIF, interferon-{gamma}–inducing factor; THIO, thioredoxin; TLTF, T lymphocyte triggering factor.


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