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 stimulate s 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-gamm a production by spleen mononuclear cells (MNC), In vivo blocking of IF N-gamma by intraperitoneal injection of mouse monoclonal anti-IFN-gamm a antibody suppressed parasite growth and increased survival of both C 3H/H3 and C57Bl/6J animals, suggesting that, irrespective of strain-re lated disease susceptibility, IFN-gamma is a growth-promoting stimulus for T. b. brucei, Spleen MNC from noninfected mice of all strains wer e in vitro likewise strongly induced to IFN-gamma production when expo sed to TLTF. This suggests that CD8(+) expressing T cell receptor (TCR ) alpha/beta, gamma/delta-bearing T cells and NK cells may all be trig gered to IFN-gamma production by TLTF. In all mouse strains, TLTF also caused an increase in the number of cells expressing mRNA for TGF-bet a in vitro, However, significant triggering to IL-4 mRNA expression on ly 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 d egree of resistance may be related to inherent strain ability to produ ce IL-4 in response to TLTF.