LEISHMANIA-MAJOR - A CLONE WITH LOW VIRULENCE FOR BALB C MICE ELICITSA TH1 TYPE RESPONSE AND PROTECTS AGAINST INFECTION WITH A HIGHLY VIRULENT CLONE/

BALB/c mice are highly susceptible to infection with Leishmania major and generally develop a severe, nonhealing form of disease following p arasite inoculation. As opposed to protective Th1 type immune response s which develop in resistant strains of mice, BALB/c mice develop pred ominant Th2 type responses characterized by the production of high lev els of IL-4, but only low levels of IFN-gamma. However, BALB/c mice wi ll develop resistance and Th1 type responses following the inoculation of very low numbers of L. major-promastigotes. In this study, we have examined the effects of parasite virulence on the immune response and disease phenotype in susceptible BALB/c mice. Two clones of L. major were isolated which differed with respect to their in vitro growth rat es as promastigotes and their virulence for mice. One rapidly growing clone, L.m.F1, was highly virulent in BALB/c mice and produced nonheal ing infections characterized by predominant Th2 type responses. In con trast, a slow-growing clone, L.m.S2, was less virulent in BALB/c mice and produced self-healing infections at parasite doses equivalent to t hose which produced progressive disease with the more virulent clone. Mice which healed infections with the L.m.S2 clone developed responses characterized by elevated production of IFN-gamma and were resistant to a challenge infection with the virulent L.m.F1 clone. These results suggest that the virulence of individual parasite clones may influenc e both the course of disease and the phenotype of the immune response which develops during infection. (C) 1997 Academic Press.