Carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1) negatively regulates T cell function. CEACAM1 is expressed on alloreactive donor T cells upon activation, and on epithelial and endothelial cells. We examined its role in acute graft-versus-host-disease (GVHD) after experimental allogeneic bone marrow transplantation (allo-BMT).
CEACAM1-/- donor T cells caused increased mortality and large intestinal GVHD, and showed increased activation and expression of gut-trafficking molecules, a partial defect in anergy induction, and increased accumulation in the intestines. By contrast, CEACAM1-overexpressing donor T cells caused significantly less GVHD mortality and damage to the liver, small and large intestines, and thymus, which correlated with decreased organ infiltration.
Ceacam1-/- BMT recipients had increased systemic and large intestinal GVHD. Donor T cells had increased activation and accumulation in the intestines. Additionally, Ceacam1 /- mice were also radiation-sensitive, with increased mortality and damage to intestinal crypts after irradiation.
We conclude that CEACAM1 is an important regulator of acute GVHD and radiation-containing BMT conditioning regimens, and may serve as a potential therapeutic target for the prophylaxis or treatment of GVHD.
