CD99-dependent expansion of myeloid-derived suppressor cells and attenuation of graft-versus-host disease

Mol Cells. 2012 Mar;33(3):259-67. doi: 10.1007/s10059-012-2227-z. Epub 2012 Feb 15.


CD99 is involved in many cellular events, such as the generation of Hodgkin and Reed-Sternberg cells, T cell costimulation, and leukocyte transendothelial migration. However, these studies have been limited to in vitro or in vivo experiments using CD99-deficient cell lines or anti-CD99 antibodies. In the present study, using CD99-deficient mice established by the exchangeable gene trap method, we investigated the physiologic function of murine CD99. In a B6 splenocytes → bm12 graft-versus-host disease model, wild-type cells were minimally lethal, whereas all mice that received CD99-deficient donor cells developed an early and more severe pathology. Graftversus-host disease in these mice was associated with insufficient expansion of myeloid-derived suppressor cells. This was confirmed by experiments illustrating that the injection of wild-type donor cells depleted of Mac-1(+) cells led to an almost identical disease course as the CD99-deficient donor system. Therefore, these results suggest that CD99 plays a crucial role in the attenuation of graft-versus-host disease by regulating the expansion of myeloid-derived suppressor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 12E7 Antigen
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Cell Movement
  • Cell Proliferation*
  • Cell Transplantation / adverse effects
  • Cytokines / blood
  • Graft vs Host Disease / metabolism*
  • Graft vs Host Disease / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloid Cells / metabolism
  • Myeloid Cells / physiology*
  • Neoplasm Transplantation / pathology
  • Spleen / immunology
  • Spleen / pathology


  • 12E7 Antigen
  • Antigens, CD
  • Cd99 protein, mouse
  • Cytokines