Schistosome-infected IL-4 receptor knockout (KO) mice, in contrast to IL-4KO mice, fail to develop granulomatous pathology while maintaining the same lymphokine expression profile

Th2 lymphocytes have been postulated to play a major role in the immunopath ology induced by Schistosoma mansoni-infection, Nevertheless, infected IL-4 knockout (KO) and wild-type (wt) mice develop egg granulomas comparable in size, To further investigate the function of the Th2 response in egg patho logy we studied IL-4R alpha-deficient mice, which are nonresponsive to both IL-4 and IL-13, In striking contrast to IL-4 KO animals, infected IL-4R al pha KO mice developed only minimal hepatic granulomas and fibrosis despite the presence of CD3(+) T cells in the residual egg lesions. Moreover, liver lymphokine mRNA levels in these animals and IL-4 KO mice were equivalent. In addition, infected IL-4R alpha-deficient, IL-4-deficient, and wt animals developed similar egg Ag-specific IgG Ab titers, arguing that CD4-dependen t Th activity is intact in KO mice, As expected, IFN-gamma secretion was st rongly up-regulated in mesenteric lymph node cultures from both groups of d eficient animals, a change reflected in increased serum IgG2a and IgG2b Ab levels; Surprisingly, Th2 cytokine production in infected IL-4Ra! KO mice w as not abolished but was only reduced and resembled that previously documen ted in IL-4 KO animals. This residual Th2 response is likely to explain the ability of IL-4 KO mice to generate egg granulomas, which cannot be formed in IL-4R alpha-deficient animals because of their lack of responsiveness t o the same cytokine ligands, Taken together, these findings argue that tiss ue pathology in schistosomiasis requires, in addition to egg-specific CD4() lymphocytes, a previously unrecognized IL-4R alpha(+) non-T cell effector population.