%0 Journal Article
%T Th17 Mediated Alloreactivity Is Facilitated by the Pre-Transplant Microbial Burden of the Recipient
%A Aleksandra Klimczak
%A Andrzej Lange
%J Bone Marrow Research
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/960280
%X Acute graft-versus-host disease (aGvHD) is a major complication after hematopoietic stem cell transplantation (HSCT) and severity of aGvHD is associated with biological and genetic factors related to donors and recipients. Studies on inflammatory pathways involved in aGvHD have shown a significant impact of the gut microflora on aGvHD development giving increasing evidence in the understanding of the response of innate and adaptive immunity to microbial products. Cytokine deregulation may increase or reduce the risk of aGvHD. Damage of tissues affected by aGvHD reflects the immunological cascade of events in this disease. 1. Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is a clinically accepted procedure in some hematological malignances, aplastic anemia, and inborn errors. It is rather a complex procedure, associated with both the adverse effect aGvHD and with the presence of beneficial alloreactivity, as it is graft versus leukemia or versus cells with inborn error reaction [1¨C4]. Alloreactivity influences both hematological and immunological recovery. Both alloreactivity and recovery of blood cells take place in an environment full of microbial agents in a latent form or colonizing/invading the host. Innate and adaptive immunity competence prior to and after HSCT secure an event-free course after HSCT with respect to that. 1.1. Biology of Acute GvHD Damage of the gastrointestinal tract during the acute phase of GvHD plays a major pathophysiological role in the amplification of this systemic disease. Several experimental and clinical observations highlight the role of effector cells of the immune system migration into the skin and gastrointestinal tract in the pathobiology of aGvHD [5]. Mice are the most often used animal model of GvHD. Differences in age, sex, genetic matching, and also gut microbiota of the mice are found to be the main players in pathophysiology of GvHD [6]. One of the first reports describing the microbial environment of the recipient as an important cofactor of gut aGvHD development was presented by Van Bekkum et al. [7, 8]. In their studies they compared the fate of conventionally and germ-free housed mice after whole-body irradiation and MHC incompatible bone marrow cell transplantation. Enteric aGvHD was less frequent in germ-free mice and in mice receiving antibiotic prophylaxis as compared to conventionally transplanted animals. The authors concluded that antigenic epitopes of microorganisms shared with gut epithelial cells may promote alloreactivity. These observations indicated that lymphocytes
%U http://www.hindawi.com/journals/bmr/2012/960280/