T. brucei brucei released a lymphocyte triggering factor (TLTF), which triggered purified CD8+, but not CD4+, T cells to interferon y (IFN-T) mRNA expression and secretion and to rH] thymldine incorporation. TLTF also induced mRNA for transforming growth factor 8, but not for interleukin-4. The action of this TLTF on mononuclear cell (MNC) cultures was blocked by anti-CD8 antibodies and by soluble CD8. MNCs from a mutant mouse strain lacking CD8 expression were not triggered by TLTF. IFN-1 provides a growth stimulus for T. brucei brucei, and infected CD8-mice had much lower parasitemiaand survived longerthan CD8+ mice. The host-parasite interaction in experimental African trypanosomiasis thus involves parasite release of TLTF, which by binding to CD8 triggers CD8+ cells to produce the parasite growth-promoting cytokine IFN-y.