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*
Immunobiology Section, Laboratory of Parasitic Diseases, and
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Animal Science Branch, National Cancer Institute, National Institutes of Health, Frederick, MD 21702; and
§
Biomedical Research Institute, Rockville, MD 20852
Th2 lymphocytes have been postulated to play a major role in the
immunopathology 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 pathology we studied
IL-4R
-deficient mice, which are nonresponsive to both IL-4 and
IL-13. In striking contrast to IL-4 KO animals, infected IL-4R 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-deficient,
IL-4-deficient, and wt animals developed similar egg Ag-specific IgG Ab
titers, arguing that CD4-dependent Th activity is intact in KO mice. As
expected, IFN-
secretion was strongly up-regulated in mesenteric
lymph node cultures from both groups of deficient animals, a change
reflected in increased serum IgG2a and IgG2b Ab levels. Surprisingly,
Th2 cytokine production in infected IL-4R KO mice was not abolished
but was only reduced and resembled that previously documented 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-deficient animals because of their lack of responsiveness to
the same cytokine ligands. Taken together, these findings argue that
tissue pathology in schistosomiasis requires, in addition to
egg-specific CD4+ lymphocytes, a previously unrecognized
IL-4R+ non-T cell effector
population.
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