The switching mechanisms of the phenotype of murine chronic Graft-versus-Host Disease from SLE type to SSc type.

2013 Fiscal Year Final Research Report

• Project/Area Number: 24700438
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: Tokyo University of Science
• Principal Investigator: OGAWA Shuuhei 東京理科大学, 生命医科学研究所, 助教 (20385553)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 疾患モデル / 全身性強皮症動物モデル / GVH病 / T細胞 / CD28 / 補助シグナル / 制御性T細胞

Research Abstract

In patients receiving allogeneic hematopoietic cell transplantation (HCT), chronic graft-versus-host disease (cGVHD) resembles autoimmune diseases such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). In this study, we investigated the function of host T cells on symptoms in cGVHD. CD28-deficient mice as hosts showed an SSc-type cGVHD phenotype; in contrast, WT hosts showed an SLE-type cGVHD phenotype. Adoptive cell transfer experiments demonstrated that defects in host CD4+CD25+ Treg, but not in conventional CD4+ T cells were responsible for phenotypic conversion. Furthermore, the defect of host Treg cells altered the cytokine pattern of donor CD4+ T cells might lead to phenotypic change of cGVHD. Thus, host's CD28 signaling, particularly the pathway that drives Treg development, and host Treg cells played a protective role of the development of SSc-type cGVHD.

Research Products

• [Journal Article] Quantitative analysis by surface plasmon resonance of CD28 interaction with cytoplasmic adaptor molecules Grb2, Gads and p85 PI3K (2014)
  • Author(s): Higo, K., Oda, M., Morii, H., Takahashi, J., Harada, Y., Ogawa, S., and Abe, R.
  • Journal Title: Immunol Invest. Volume: 43 Pages: 278-291
  • Peer Reviewed
• [Journal Article] CD28 signaling in primary CD4+ T cells : Identification of both tyrosine phosphorylation-dependent and independent pathway (2013)
  • Author(s): Ogawa, S., Ito, N., Watanabe, S., Watanabe, M., Inutake, Y., Sakurai, Y., Harada, Y., Kishimoto H., and Abe, R.
  • Journal Title: Int. Immunol. Volume: 25 Pages: 671-681
  • Peer Reviewed
• [Journal Article] AP-1 transcription factor is involved in ICOS gene expression downstream of TCR/CD28 signaling and cytokine receptor signaling (2012)
  • Author(s): Watanabe, M., Nakajima, S, Ohnuki, K., Ogawa S., Yamashita, M., Nakayama, T., Murakami Y., Tanabe, K. and Abe, R.
  • Journal Title: European Journal Immunology Volume: 42(7) Pages: 1850-62
  • Peer Reviewed
• [Presentation] The condition of host CD4+Cd25+ regulatory T cells determines the phenotype of chronic Graft-versus-Host Disease (2013)
  • Author(s): Akieda, Y., Nakamura, T., Wakamatsu, E., Ogawa, S., Watanabe, S., and Abe, R.
  • Organizer: Annual Meeting of The Japanese Society for Immunology, 2013
  • Place of Presentation: Makuhari Messe, Chiba
  • Year and Date: 20131211-13
• [Presentation] The behavior of cytokines determines the cGVHD phenotype (2013)
  • Author(s): Nakamura, T., Akieda, Y., Ogawa, S., Watanabe, S., Wakamatsu, E., and Abe, R.
  • Organizer: Annual Meeting of The Japanese Society for Immunology, 2013
  • Place of Presentation: Makuhari Messe, Chiba
  • Year and Date: 20131211-13
• [Presentation] Differential requirement for CD28 cytoplasmic motifs in T cell responses (2013)
  • Author(s): Ogawa, S., Yoshida, N., Sano, S., Ohtsuka, S., Nakamura, T., Akieda, Y., Watanabe, S., and Abe, R.
  • Organizer: Annual Meeting of The Japanese Society for Immunology, 2013
  • Place of Presentation: Makuhari Messe, Chiba
  • Year and Date: 20131211-13
• [Remarks]
  • URL: http://www.ribs.tus.ac.jp/immunology/