IMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE

Transplantation of allogeneic hematopoietic stem cells is the only curative option for a number of diseases of hematopoietic system. It is intended to replace the hematopoietic system of the recipient withthe donor’s. However, when mature T cells contained in the graft enter the recipient organism,...

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Autores principales:	G. A. Efimov, A. S. Vdovin, A. A. Grigoryev, S. Yu. Filkin, N. A. Bykova, V. G. Savchenko
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2016
Materias:	graft-versus-tumor reaction graft-versus-host disease bone marrow transplantation alloreactivity immunobiology molecular mechanisms Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/5d2db2ba6c2549c7906c02be3e891917
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spelling	oai:doaj.org-article:5d2db2ba6c2549c7906c02be3e8919172021-11-18T08:03:45ZIMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE1563-06252313-741X10.15789/1563-0625-2015-6-499-516https://doaj.org/article/5d2db2ba6c2549c7906c02be3e8919172016-01-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/958https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XTransplantation of allogeneic hematopoietic stem cells is the only curative option for a number of diseases of hematopoietic system. It is intended to replace the hematopoietic system of the recipient withthe donor’s. However, when mature T cells contained in the graft enter the recipient organism, it may lead to a severe post-transplant complication, the “graft versus host” disease (GVHD). It occurs due to the fact that the donor immune system contains T cell clones specific to recipient alloantigens. These cell clones are activated upon encountering their antigens, thus causing systemic damage to healthy tissues. Development of the alloreactive clones is caused by genetic differences between donor and recipient. The most importantfactors determining successful transplantation concern the compatibility for the genes coding for Major Histocompatibility Complex (MHC), that are expressed in all nucleated cells and are responsible for antigen presentation to the immune cells. Currently established extensive donor banks allow for majority of patients to choose a compatible donor. However, this does not provide complete prevention of the GVHD development, because in addition to the MHC genes the donor and recipient may differ in so-called minor histocompatibility antigens. Minor antigens may be caused by genetic polymorphisms in all of the genome coding regions. Pre-transplantation conditioning of the patient, which is necessary for engraftment represent an additional factor contributing to the GVHDdevelopment, since as its side effect it leads to formation of a pro-inflammatory environment in the organism of recipient. Severe GVHD develops in approximately 40% of MHC-matched patients, while in cases of partial compatibility this proportion is even higher. GVHD causes mortality comparable to other causes of posttransplantdeath, such as viral infections or relapse of underlying disease. Thus, the development of severe GVHD is a significant limitation for clinical applications of stem cell transplantation. Severe immunesuppression or depletion of mature donor T cells from the transplant leads to increased probability of relapse and weakens anti-infectious immunity. Hence, further search for alternative, more specific ways to prevent GVHD is required. This review will focus on the mechanisms of alloreactive T lymphocyte clone development and key pathogenetic stages of acute “graft versus host” disease.G. A. EfimovA. S. VdovinA. A. GrigoryevS. Yu. FilkinN. A. BykovaV. G. SavchenkoSPb RAACIarticlegraft-versus-tumor reactiongraft-versus-host diseasebone marrow transplantationalloreactivityimmunobiologymolecular mechanismsImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 17, Iss 6, Pp 499-516 (2016)
institution	DOAJ
collection	DOAJ
language	RU
topic	graft-versus-tumor reaction graft-versus-host disease bone marrow transplantation alloreactivity immunobiology molecular mechanisms Immunologic diseases. Allergy RC581-607
spellingShingle	graft-versus-tumor reaction graft-versus-host disease bone marrow transplantation alloreactivity immunobiology molecular mechanisms Immunologic diseases. Allergy RC581-607 G. A. Efimov A. S. Vdovin A. A. Grigoryev S. Yu. Filkin N. A. Bykova V. G. Savchenko IMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE
description	Transplantation of allogeneic hematopoietic stem cells is the only curative option for a number of diseases of hematopoietic system. It is intended to replace the hematopoietic system of the recipient withthe donor’s. However, when mature T cells contained in the graft enter the recipient organism, it may lead to a severe post-transplant complication, the “graft versus host” disease (GVHD). It occurs due to the fact that the donor immune system contains T cell clones specific to recipient alloantigens. These cell clones are activated upon encountering their antigens, thus causing systemic damage to healthy tissues. Development of the alloreactive clones is caused by genetic differences between donor and recipient. The most importantfactors determining successful transplantation concern the compatibility for the genes coding for Major Histocompatibility Complex (MHC), that are expressed in all nucleated cells and are responsible for antigen presentation to the immune cells. Currently established extensive donor banks allow for majority of patients to choose a compatible donor. However, this does not provide complete prevention of the GVHD development, because in addition to the MHC genes the donor and recipient may differ in so-called minor histocompatibility antigens. Minor antigens may be caused by genetic polymorphisms in all of the genome coding regions. Pre-transplantation conditioning of the patient, which is necessary for engraftment represent an additional factor contributing to the GVHDdevelopment, since as its side effect it leads to formation of a pro-inflammatory environment in the organism of recipient. Severe GVHD develops in approximately 40% of MHC-matched patients, while in cases of partial compatibility this proportion is even higher. GVHD causes mortality comparable to other causes of posttransplantdeath, such as viral infections or relapse of underlying disease. Thus, the development of severe GVHD is a significant limitation for clinical applications of stem cell transplantation. Severe immunesuppression or depletion of mature donor T cells from the transplant leads to increased probability of relapse and weakens anti-infectious immunity. Hence, further search for alternative, more specific ways to prevent GVHD is required. This review will focus on the mechanisms of alloreactive T lymphocyte clone development and key pathogenetic stages of acute “graft versus host” disease.
format	article
author	G. A. Efimov A. S. Vdovin A. A. Grigoryev S. Yu. Filkin N. A. Bykova V. G. Savchenko
author_facet	G. A. Efimov A. S. Vdovin A. A. Grigoryev S. Yu. Filkin N. A. Bykova V. G. Savchenko
author_sort	G. A. Efimov
title	IMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE
title_short	IMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE
title_full	IMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE
title_fullStr	IMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE
title_full_unstemmed	IMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE
title_sort	immunobiology of acute graft-versus-host disease
publisher	SPb RAACI
publishDate	2016
url	https://doaj.org/article/5d2db2ba6c2549c7906c02be3e891917
work_keys_str_mv	AT gaefimov immunobiologyofacutegraftversushostdisease AT asvdovin immunobiologyofacutegraftversushostdisease AT aagrigoryev immunobiologyofacutegraftversushostdisease AT syufilkin immunobiologyofacutegraftversushostdisease AT nabykova immunobiologyofacutegraftversushostdisease AT vgsavchenko immunobiologyofacutegraftversushostdisease
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IMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE

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