Fluctuations in pathogenic CD4+ T-cell subsets in a murine sclerodermatous model of chronic graft-versus-host disease.

To determine the roles of CD4+ T-cell (Th) subsets, including Th17 cells, in the development of chronic graft-versus-host disease (cGVHD), we used a Th-dependent cGVHD model comprising B10.D2 donor and BALB/c recipient mice. The clinical GVHD score increased beginning at day +14, peaked at day +42, and remained elevated until day +70. In the skin, increased dermal thickness was apparent at day +14, and maintained with few changes until day +70. In contrast, the liver had peak pathologic scores at day +28, and the tissue damage began to improve at day +56. To determine possible associations between improvement of liver pathology and changes in Th subsets, we analyzed Th subsets using flow cytometry. Th1 frequencies in the livers were greater than other Th subsets throughout the disease course, but the frequencies decreased over time. Notably, Th17 cells were rarely detected during earlier periods, but emerged at day +56, which correlated with the improved hepatic inflammation. In contrast, other Th subsets (Th2 and regulatory T cells) did not change significantly during the disease course. These results indicate the association of attenuation on cGVHD with a later emergence of Th17 cells and concomitant decrease of Th1 cells.