The gene for a T lymphocyte triggering factor from African trypanosomes.
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.
Vaidya
T
T
Department of Biochemistry, University of Iowa, and the Howard Hughes Medical Institute, Iowa City, Iowa 52242, USA.
Bakhiet
M
M
Hill
K L
KL
Olsson
T
T
Kristensson
K
K
Donelson
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017125:Genes, Protozoan; D006801:Humans; D007369:Interferon Inducers / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D007369:Interferon Inducers; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C107172:T lymphocyte triggering factor, Trypanosoma brucei; D007371:Interferon-gamma