Helper T-cell differentiation in graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Arch Immunol Ther Exp (Warsz) 2014 Aug;62(4):277-301
Date
04/05/2014Pubmed ID
24699629DOI
10.1007/s00005-014-0284-zScopus ID
2-s2.0-84904287693 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapeutic option for many malignant diseases. However, the efficacy of allo-HSCT is limited by the occurrence of destructive graft-versus-host disease (GVHD). Since allogeneic T cells are the driving force in the development of GVHD, their activation, proliferation, and differentiation are key factors to understanding GVHD pathogenesis. This review focuses on one critical aspect: the differentiation and function of helper T (Th) cells in acute GVHD. We first summarize well-established subsets including Th1, Th2, Th17, and T-regulatory cells; their flexibility, plasticity, and epigenetic modification; and newly identified subsets including Th9, Th22, and T follicular helper cells. Next, we extensively discuss preclinical findings of Th-cell lineages in GVHD: the networks of transcription factors involved in differentiation, the cytokine and signaling requirements for development, the reciprocal differentiation features, and the regulation of microRNAs on T-cell differentiation. Finally, we briefly summarize the recent findings on the roles of T-cell subsets in clinical GVHD and ongoing strategies to modify T-cell differentiation for controlling GVHD in patients. We believe further exploration and understanding of the immunobiology of T-cell differentiation in GVHD will expand therapeutic options for the continuing success of allo-HSCT.
Author List
Fu J, Heinrichs J, Yu XZAuthor
Xue-Zhong Yu MD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Differentiation
Graft vs Host Disease
Hematopoiesis
Hematopoietic Stem Cell Transplantation
Humans
Postoperative Complications
T-Lymphocyte Subsets
T-Lymphocytes, Helper-Inducer
Transplantation, Homologous