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

Journal of Immunology, ISSN: 0022-1767, Vol: 163, Issue: 1, Page: 337-342
1999
  • 136
    Citations
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  • 46
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Metrics Details

  • Citations
    136
    • Citation Indexes
      136
  • Captures
    46

Article Description

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-4Rα-deficient mice, which are nonresponsive to both IL-4 and IL-13. In striking contrast to IL-4 KO animals, infected IL- 4Rα 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-4Rα-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-γ 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-4Rα 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- 4Rα-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-4Rα non-T cell effector population.

Bibliographic Details

Dragana Jankovic; Marika C. Kullberg; Patricia Caspar; Allen W. Cheever; Alan Sher; Nancy Noben-Trauth; William E. Paul; Jerrold M. Ward

Oxford University Press (OUP)

Medicine; Immunology and Microbiology

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