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IL-4 expression by grafts from transgenic mice fails to prevent allograft rejection.
Mueller, R; Davies, J D; Krahl, T; Sarvetnick, N.
Afiliación
  • Mueller R; Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Immunol ; 159(4): 1599-603, 1997 Aug 15.
Article en En | MEDLINE | ID: mdl-9257818
Cell-mediated tissue destruction, such as that occurring in allograft rejection, is thought to be mediated by Th1 cells and cytokines. We have recently shown that transgenic expression of the Th2 cytokine IL-4 by pancreatic beta cells completely protects nonobese diabetic (NOD) mice from autoimmune diabetes by inducing functional tolerance among autoreactive T cells. To investigate whether local IL-4 production could also induce functional tolerance among alloreactive T cells and thus prevent allograft rejection, we transplanted pancreata from transgenic neonatal mice and their nontransgenic littermates into allogeneic hosts. Within 2 wk, recipient mice had rejected their grafts regardless of the transgene's presence or absence. Considering that the vigorous immune response induced might have prevented any effect by IL-4, we injected recipient mice with anti-CD4 and anti-CD8 mAbs, thereby depleting them of T cells and thus providing the islets with an opportunity to mature and grow. This approach indeed delayed rejection of neonatal pancreata from nontransgenic mice by >1 wk. By that time, however, pancreata from transgenic mice had also been rejected. Our results indicate that the allograft rejection response under these conditions, in contrast to the autoimmune response in NOD mice, cannot be regulated by local IL-4 production, regardless of the cytokine's impact on Th1 cells.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-4 / Trasplante de Páncreas / Rechazo de Injerto Límite: Animals Idioma: En Revista: J Immunol Año: 1997 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-4 / Trasplante de Páncreas / Rechazo de Injerto Límite: Animals Idioma: En Revista: J Immunol Año: 1997 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos