Linked in vivo expression of soluble interleukin-4 receptor and interleukin-4 in murine schistosomiasis.
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 synthesis is consistent with a potential role for sIL-4R in the regulation of IL-4 activity in vivo.
Fernandez-Botran
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R
Department of Pathology, School of Medicine, University of Louisville, KY 40292, USA.
Wynn
T A
TA
Hieny
S
S
Caspar
P
P
Chilton
P M
PM
Sher
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D005260:Female; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D008099:Liver / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D018123:Receptors, Interleukin; D015847:Interleukin-4