In spite of considerable therapeutic progress, acute graft--host disease still limits allogeneic hematopoietic cell transplantation. We recently reported that mouse infection with nidovirus lactate dehydrogenase elevating virus impairs disease in non-conditioned B6D2F1 recipients of parental B6 spleen cells. As this virus activates TLR7, we tested a pharmacological TLR7 ligand, R848, in this model and observed complete survival if donor and recipients were treated before transplantation.
View Article and Find Full Text PDFIntroduction: Viruses have developed multiple mechanisms to alter immune reactions. In 1969, it was reported that lactate dehydrogenase-elevating virus (LDV), a single stranded positive sense mouse nidovirus, delays skin allograft rejection and inhibits spleen alterations in graft versus host disease (GVHD). As the underlying mechanisms have remained unresolved and given the need for new therapies of this disease, we reassessed the effects of the virus on GVHD and tried to uncover its mode of action.
View Article and Find Full Text PDFAcute graft versus host disease (aGVHD) remains a life-threatening complication of bone marrow transplantation. Here we show that IL-27, a member of the IL-12 cytokine family, plays an essential role in a parent-to-F1 murine aGVHD model, using B6 mice as parents and B6D2 mice as F1 recipients. IL-27 is transiently detectable in the serum of B6D2 recipients of B6 spleen cells, with a peak at day 10.
View Article and Find Full Text PDFAnticytokine auto-vaccination is a powerful tool for the study of cytokine functions in vivo but has remained rather esoteric as a result of numerous technical difficulties. We here describe a two-step procedure based on the use of OVA multimers purified by size exclusion chromatography after incubation with glutaraldehyde at pH 6. When such polymers are incubated with a target protein at pH 8.
View Article and Find Full Text PDFIL-4Ralpha-dependent responses are essential for granuloma formation and host survival during acute schistosomiasis. Previously, we demonstrated that mice deficient for macrophage-specific IL-4Ralpha (LysM(cre)Il4ra(-/lox)) developed increased hepatotoxicity and gut inflammation; whereas inflammation was restricted to the liver of mice lacking T cell-specific IL-4Ralpha expression (iLck(cre)Il4ra(-/lox)). In the study presented here we further investigated their role in liver granulomatous inflammation.
View Article and Find Full Text PDFInterleukin-(IL)-4 and IL-13 signal through heterodimeric receptors containing a common IL-4 receptor-alpha (IL-4Ralpha) subunit, which is important for protection against helminth infections, including schistosomiasis. Previous studies demonstrated important roles for IL-4Ralpha-responsive hematopoietic cells, including T cells and macrophages in schistosomiasis. In this study, we examined the role of IL-4Ralpha responsiveness by nonhematopoietic smooth muscle cells during experimental acute murine schistosomiasis.
View Article and Find Full Text PDFInterleukin (IL)-4 and IL-13 are T helper 2 cytokines whose biological functions are induced through a common IL-4 receptor alpha chain (IL-4Ralpha). CD4(+) T cell-specific IL-4Ralpha-mediated signaling drives susceptibility to Leishmania major infection, but is not essential to host survival following Schistosoma mansoni infection. Here we generated a novel mouse model lacking IL-4Ralpha expression specifically on all T cells (iLck(cre)Il4ra(-/lox)), which was compared with CD4(+) T cell-specific IL-4Ralpha-deficient mice (Lck(cre)Il4ra(-/lox)), to investigate the possible roles of IL-4Ralpha responsive non-CD4(+) T cells during either L.
View Article and Find Full Text PDFBackground: Intestinal mucus production by hyperplasic goblet cells is a striking pathological feature of many parasitic helminth infections and is related to intestinal protection and worm expulsion. Induction of goblet cell hyperplasia is associated with TH2 immune responses, which in helminth infections are controlled primarily by IL-13, and also IL-4. In the study presented here we examine the goblet cell hyperplasic response to three experimental parasitic helminth infections; namely Nippostrongylus brasiliensis, Syphacia obvelata and Schistosoma mansoni.
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