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Linked in vivo expression of soluble interleukin‐4 receptor and interleukin‐4 in murine schistosomiasis
Author(s) -
FernandezBotran Rafael,
Wynn Thomas A.,
Hieny Sara,
Caspar Patricia,
Chilton Paula M.,
Sher Alan
Publication year - 1995
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830250304
Subject(s) - biology , in vivo , splenocyte , immune system , immunology , antigen , spleen , receptor , interleukin 2 , secretion , antibody , schistosoma mansoni , interleukin 4 , interleukin , microbiology and biotechnology , cytokine , endocrinology , schistosomiasis , biochemistry , helminths
Abstract Soluble interleukin‐4 receptors (sIL‐4R) are truncated IL‐4R molecules that are secreted into biological fluids. To gain an insight into the mechanisms that control sIL‐4R synthesis in vivo and their role in the regulation of immune responses, the expression and secretion of sIL‐4R in mice infected with Schistosoma mansoni was studied. Splenocytes from infected animals responded to schistosomal antigen preparations with increased production of both IL‐4 and sIL‐4R. The synthesis of sIL‐4R by spleen cells peaked at 8 weeks following infection and coincided with maximum levels of sIL‐4R in serum and sIL‐4R‐specific mRNA in the liver of infected mice. The expression of IL‐4‐specific mRNA in the liver was different from that of IL‐4R, reaching its peak approximately 2 weeks earlier. A relationship between sIL‐4R production and the development and activation of Th2 cells was suggested by the findings that: (a) in vivo administration of anti‐IL‐4 antibodies (11B11) impaired the ability of splenic cells to secrete either IL‐4 or sIL‐4R; and (b) splenic cells from mice vaccinated with irradiated cercariae, which tend to develop much weaker Th2 responses than mice injected with live cercariae, expressed reduced levels of sIL‐4R when challenged with schistosomal antigens. Moreover, a direct role for IL‐4 in regulating the expression of sIL‐4R was suggested by the ability of anti‐IL‐4 antibodies to inhibit sIL‐4R synthesis in vitro . These data provide the first evidence demonstrating that the production of sIL‐4R in vivo is up‐regulated during immune responses, especially during those characterized by the development and activation of Th2 cells and IL‐4 secretion. The association between sIL‐4R and IL‐4 syntheses is consistent with a potential role for sIL‐4R in the regulation of IL‐4 activity in vivo .