Dynamic regulation of effector IFN-γ-producing and IL-17-producing T cell subsets in the development of acute graft-versus-host disease

Zhao,Kai; Ruan,Suhong; Yin,Lingling; Zhao,Dongmei; Chen,Chong; Pan,Bin; Zeng,Lingyu; Li,Zhenyu; Xu,Kailin

doi:10.3892/mmr.2015.4638

Dynamic regulation of effector IFN-γ-producing and IL-17-producing T cell subsets in the development of acute graft-versus-host disease

Authors:
- Kai Zhao
- Suhong Ruan
- Lingling Yin
- Dongmei Zhao
- Chong Chen
- Bin Pan
- Lingyu Zeng
- Zhenyu Li
- Kailin Xu
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Affiliations: Key Laboratory of Bone Marrow Stem Cell, Xuzhou, Jiangsu 221002, P.R. China, Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China
Published online on: December 4, 2015 https://doi.org/10.3892/mmr.2015.4638
Pages: 1395-1403

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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.

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