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 KINASE-A

Trypanosoma brucei brucei releases a lymphocyte-triggering factor (TLT F) that activates CD8+ T cells. We here study second messenger mechani sms in this activation, i. e. the effects of protein kinase C (PKC), p rotein kinase A (PKA) and tyrosine kinases (TPK) inhibitors on TLTF-in duced interferon-gamma (IFN-gamma) secretion and proliferation in lymp hoid cell cultures. The effects were compared to those obtained by phy tohemagglutinin (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 P KC and the PKA inhibitors suppressed PHA-induced IFN-gamma secretion a nd proliferation of rat MNC and mouse CD8+CD4- MNC, they had no effect on the same TLTF-induced responses. The TPK inhibitor genistein, howe ver, strongly suppressed TLTF-induced activation of both types of resp onder cells to IFN-gamma secretion and the TLTF-induced proliferation of mouse CD8+CD4- MNC. The suppressive effects of the drugs could be o vercome 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 o ther than the PKC- or PKA-dependent signal transduction, and that TPK may be involved in the triggering.