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

摘要

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-.-producing and IL-17-producing effector T cells remain unclear. The present study aimed to investigate the dynamic changes of alloantigenspecific 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-gamma(+)CD8(+) T (Tc1) cells were detected in the early stage of GVHD. The differentiation of CD4(+) T cells into Th1 cell (IFN-gamma(+)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-.) 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.