Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation

PLoS One. 2011;6(7):e21611. doi: 10.1371/journal.pone.0021611. Epub 2011 Jul 6.


Background: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.

Methods: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In vivo, Ceacam1(-/-) T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi), CD62L(lo)). Additionally, Ceacam1(-/-) CD8 T cells had greater expression of the gut-trafficking integrin α(4)β(7), though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/-) recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/-) mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+) lymphoma model was improved in animals receiving Ceacam1(-/-) vs. control T cells.

Conclusions: We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the donor graft and host tissues, this suggests that targeting Ceacam1 may represent a potent strategy for the regulation of GVHD and GVT after allogeneic transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Transplantation / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / radiation effects
  • Carcinoembryonic Antigen / metabolism*
  • Cell Polarity / radiation effects
  • Cell Proliferation / radiation effects
  • Cytotoxicity, Immunologic / radiation effects
  • Dendritic Cells / immunology
  • Dendritic Cells / radiation effects
  • Graft vs Host Disease / complications
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / mortality
  • Graft vs Tumor Effect / immunology*
  • Graft vs Tumor Effect / radiation effects
  • Humans
  • Integrins / metabolism
  • Intestine, Small / pathology
  • Intestine, Small / radiation effects
  • Lymphocyte Activation / immunology
  • Lymphocyte Activation / radiation effects
  • Lymphocyte Count
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / radiation effects
  • Mice
  • Organ Specificity / immunology
  • Organ Specificity / radiation effects
  • Radiation Injuries, Experimental / complications
  • Radiation Injuries, Experimental / metabolism
  • Radiation Injuries, Experimental / pathology
  • Radiation, Ionizing
  • Transplantation, Homologous


  • Carcinoembryonic Antigen
  • Ceacam1 protein, mouse
  • Integrins
  • integrin alpha4beta7