Induction of interferon-gamma, transforming growth factor-beta, and interleukin-4 in mouse strains with different susceptibilities to Trypanosoma brucei brucei.

A Trypanosoma brucei brucei-derived lymphocyte triggering factor (TLTF) induced CD8+ T cells to produce IFN-gamma, which in turn stimulates parasite growth. This parasite-host interaction was studied in mouse strains that are either relatively susceptible (C3H/He) or resistant (C57Bl/6J) to infection, as well as in athymic nude mice. In all mouse strains, T. b. brucei infection caused a strong induction of IFN-gamma production by spleen mononuclear cells (MNC). In vivo blocking of IFN-gamma by intraperitoneal injection of mouse monoclonal anti-IFN-gamma antibody suppressed parasite growth and increased survival of both C3H/H3 and C57Bl/6J animals, suggesting that, irrespective of strain-related disease susceptibility, IFN-gamma is a growth-promoting stimulus for T. b. brucei. Spleen MNC from noninfected mice of all strains were in vitro like-wise strongly induced to IFN-gamma production when exposed to TLTF. This suggests that CD8+ expressing T cell receptor (TCR) alpha/beta, gamma/delta-bearing T cells and NK cells may all be triggered to IFN-gamma production by TLTF. In all mouse strains, TLTF also caused an increase in the number of cells expressing mRNA for TGF-beta in vitro. However, significant triggering to IL-4 mRNA expression only occurred in the relatively disease-resistant C57Bl/6J strain. As IL-4 is required for the synthesis and class switches of immunoglobulins, which are essential host immune defenses against T. b. brucei, the degree of resistance may be related to inherent strain ability to produce IL-4 in response to TLTF.