T cell activation by a Trypanosoma brucei brucei-derived lymphocyte triggering factor is dependent on tyrosine protein kinases but not on protein kinase C and A.
Trypanosoma brucei brucei releases a lymphocyte-triggering factor (TLTF) that activates CD8+ T cells. We here study second messenger mechanisms in this activation, i.e. the effects of protein kinase C (PKC), protein kinase A (PKA) and tyrosine kinases (TPK) inhibitors on TLTF-induced interferon-gamma (IFN-gamma) secretion and proliferation in lymphoid cell cultures. The effects were compared to those obtained by phytohemagglutinin (PHA) stimulation. Rat spleen mononuclear cells (MNC) and spleen MNC from a mutant mouse strain possessing CD8+ T cells but lacking CD4+ T cells were used as responder cells. Although both the PKC and the PKA inhibitors suppressed PHA-induced IFN-gamma secretion and proliferation of rat MNC and mouse CD8+ CD4- MNC, they had no effect on the same TLTF-induced responses. The TPK inhibitor genistein, however, strongly suppressed TLTF-induced activation of both types of responder cells to IFN-gamma secretion and the TLTF-induced proliferation of mouse CD8+ CD4- MNC. The suppressive effects of the drugs could be overcome by ionomycin and tetradecanoylphorbol acetate, which show that the effects were not due to drug nonspecific cellular toxicity of the drugs. We conclude that TLTF activates CD8+ T cells through pathways other than the PKC- or PKA-dependent signal transduction, and that TPK may be involved in the triggering.
Bakhiet
M
M
Department of Neurology, Huddinge University Hospital, Karolinska Institute, Stockholm Sweden.
Mix
E
E
Kristensson
K
K
Wigzell
H
H
Olsson
T
T
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014346:Trypanosoma brucei brucei / Q000276:immunology*
D000953:Antigens, Protozoan; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C