Cellular immune responses to the murine nematode parasite Trichuris muris. I. Differential cytokine production during acute or chronic infection

Abstract

A variety of T-cell parameters have been analysed in two H-2 compatible strains of mice, B10.BR and BALB/K, which differ in an absolute fashion in their ability to resist infection with the parasitic nematode Trichuris muris: BALB/K mice expel T. muris relatively rapidly, whereas B10.BR mice are unable to expel the parasite before the infection reaches patency. Analysis of Th1- and Th2-specific cytokines (IFN-gamma and IL-5, respectively) produced by in vitro Con A-stimulated mesenteric lymph node cells (MLNC) from infected and normal mice demonstrated that MLNC from resistant BALB/K mice produced high levels of IL-5 and low levels of IFN-gamma whilst B10.BR MLNC secreted large amounts of IFN-gamma in the relative absence of IL-5. As an in vivo correlate of in vitro IL-5 production, peripheral and tissue eosinophilia were quantified during the course of infection in the two strains of mice. No peripheral eosinophilia was observed in BALB/K or B10.BR individuals. However, a considerable intestinal eosinophilia was seen in the high IL-5-producing BALB/K mice compared to normal levels. Differences observed in cytokine profiles were not due to differential changes in the numbers of T cells within the MLN. Indeed, FACS analysis revealed a decrease in the relative percentage of CD4+ and CD8+ T cells in both strains of mice post-infection. Our results suggest that resistance to T. muris involves the preferential induction of Th cells which secrete IL-5, whilst cells of a different Th subset (IFN-gamma producing) predominate in chronically infected mice. As such, this represents the first description of a correlation between the reciprocal activation of Th cell subsets in relation to acute or chronic intestinal infection with the same parasite in the same host species.