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49 Absence of host cd137 signalling converts chronic gvhd toward acute gvhd
  1. J Kim,
  2. UJ Moon,
  3. H Kim,
  4. HR Cho and
  5. B Kwon
  1. Ulsan University Hospital, Biomedical Research Centre, Ulsan, Republic of Korea

Abstract

Background and aims CD137 functions mainly as a costimulatory molecule for T cell activation. However, its functions have been found in a variety of other immune and nonimmune cells. Transfer of BM12 CD4+ T cells into unirradiated, MHC II-mismateched C57BL/6 mice induces lupus-like chronic GVHD, which occurs because donor CD4+ T cells break host B cell tolerance with help from host CD4+ T cells.

Methods cGVHD was induced by transferring 8 × 107 cells/mouse BM12 spleen/lymph node cells into C57BL/6 and CD137-/- mice. Serum samples were collected 2 wk after disease induction and assayed by ELISA for IgG1 anti-DNA autoantibody. Mouse body weight measured two times a week. Splenocytes were harvested 10 days after disease induction. After counting the number of total spleen and analysed by flow cytometry. Pathological scores of colons and livers. Colons and livers were harvested 10 days after disease induction.

Results We found that chronic GVHD was inhibited when CD137-/- mice were used as the host in this chronic GVHD model. Instead, they exhibited evident loss of body weight, indicating that they had acute GVHD. Indeed, their splenocytes were markedly depleted and they had severe intestinal and liver GVHD. Consistent with these phenotype changes, there were increased numbers of Th1 and Th17 cells but decreased numbers of Treg cells in the spleen of CD137-/- recipient mice 10 days after disease induction.

Conclusions Our results indicate that host CD137 signalling is a key factor to determine the fate of donor CD4+ T cells during GVHD course.

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