title: Dynamic regulation of effector IFN-γ-producing and IL-17-producing T cell subsets in the development of acute graft-versus-host disease.
abstract: Graft-versus-host disease (GVHD) as the predominant complication of allogeneic hematopoietic stem cell transplantation remains to be fully understood. It is known that the cytokines produced by allogeneic reactive effector CD4+ and CD8+ T cells are involved in GVHD. However, the regulation and coordination of IFN-γ-producing and IL-17-producing effector T cells remain unclear. The present study aimed to investigate the dynamic changes of alloantigen-specific effector CD4+ T and CD8+ T cell subsets by flow cytometry, which produce inflammatory cytokines involved in the multistep GVHD pathogenesis progress. The results demonstrated that IL-17-producing CD8+ T (Tc17) cells and IFN-γ+CD8+ T (Tc1) cells were detected in the early stage of GVHD. The differentiation of CD4+ T cells into Th1 cell (IFN-γ+CD4+ T) and Th17 (IL-17+CD4+ T) cells was later than that of the Tc1 and Tc17 cells. The effector CD4+ T and CD8+ T cell subsets either became exhausted or became memory cells, exhibiting a CD62L-CD44+ phenotype following marked expansion during GVHD. Furthermore, T cell-associated type I (IL-2 and IFN-γ) and type II (IL-4 and IL-10) classical cytokines exhibited coordinated dynamic regulation. It was concluded that the differentiation of cytokine-producing Tc1 and Tc17 cells may be the key step in the initiation of GVHD, whereas CD4+ effector Th1 and Th17 cells are considered to be pathophysiological factors leading to the continuous aggravation of GVHD.
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Suhong
authors.initials: S
authors.lastname: Ruan
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Yin
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Pan
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu 221002, P.R. China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D007371:Interferon-gamma