Successful treatment of murine autoimmune cholangitis by parabiosis: Implications for hematopoietic therapy

Jing Bo Yang, Yin Hu Wang, Wei Yang, Fang Ting Lu, Hong Di Ma, Zhi Bin Zhao, Yan Jie Jia, Wei Tang, Koichi Tsuneyama, William M. Ridgway, M. Eric Gershwin, Zhe Xiong Lian

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

There is a significant unmet need in the treatment of primary biliary cirrhosis (PBC) despite significant data on the effector pathways that lead to biliary duct damage. We focused attention on a murine model of PBC, the dominant negative transforming growth factor β receptor II (Tg) mice. To further define the pathways that lead to biliary pathology in these mice, we developed Tg mice deleted of CD4 cells (CD4-/-Tg).Interestingly, these mice developed more severe cholangitis than control Tg mice. These mice, which lack CD4 cells, manifested increased levels of IFN-γ produced by effector CD8 cells. It appears that increased cholangitis is due to the absence of CD4 Treg cells. Based on these data, we parabiosed CD4-/-Tg mice with established disease at 8-9 weeks of age with C57BL/6 control mice. Such parabiotic "twins" had a significant reduction in autoimmune cholangitis, even though they had established pathology at the time of surgery. We prepared mixed bone marrow chimera mice constructed from CD4-/-Tg and CD8-/- mice and not only was cholangitis improved, but a decrease in terminally differentiated CD8+ T effector cells in the presence of wild type CD4 cells was noted. In conclusion, "correcting" the CD4 T cell subset, even in the presence of pathogenic CD8 T cells, is effective in treating autoimmune cholangitis.

Original languageEnglish (US)
Pages (from-to)108-117
Number of pages10
JournalJournal of Autoimmunity
Volume66
DOIs
StatePublished - Jan 1 2016

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Keywords

  • Bone marrow chimeric mice
  • CD4 T cells
  • Cholangitis
  • Parabiosis
  • Primary biliary cirrhosis
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Yang, J. B., Wang, Y. H., Yang, W., Lu, F. T., Ma, H. D., Zhao, Z. B., Jia, Y. J., Tang, W., Tsuneyama, K., Ridgway, W. M., Gershwin, M. E., & Lian, Z. X. (2016). Successful treatment of murine autoimmune cholangitis by parabiosis: Implications for hematopoietic therapy. Journal of Autoimmunity, 66, 108-117. https://doi.org/10.1016/j.jaut.2015.09.002