CD8+ T cell-induced intestinal pathology during GVHD (top) is absent in mice lacking the integrin CD103 (bottom).

Effector CD8+ T cells that cling to the intestine trigger graft-versus-host disease (GVHD), according to El-Asady and colleagues on page 1647. By contrast, effector T cells that pass through the intestine but do not linger—due to a lack of the integrin CD103—fail to induce disease.

GVHD is a serious complication of bone marrow transplantation in which donor-derived T cells infiltrate and attack host epithelial tissues such as skin and intestine. Intestinal injury results from attack on host epithelial cells by donor CD8+ effector T cells. Previous studies by this group showed that CD8+ T cell–mediated rejection of pancreatic islet allografts required T cell expression of the integrin CD103 whose ligand, E-selectin, is preferentially expressed on epithelial cells.

El-Asady and colleagues now show that tissue destruction in GVHD similarly requires CD103 expression on CD8+ T cells. Activated CD8+ T cells that accumulated in the intestine of host mice after allogeneic bone marrow transplant expressed CD103. Activated CD8+ T cells that migrated to other organs such as the liver or spleen, by contrast, did not express this integrin.

T cells lacking CD103 could still migrate to the intestines, but failed to accumulate there and did not trigger GVHD, indicating that development of GVHD required CD103-mediated adherence of T cells to the intestinal epithelium. The cytokine TGF-β, likely produced locally in the intestine, was the driving force behind the expression of CD103, as T cells with a defective TGF-β receptor were unable to up-regulate CD103 and accumulate in the intestine.Whether the CD103-expressing T cells induce GVHD directly or indirectly is not yet clear. The authors suspect the latter and propose that CD103-mediated adhesion allows the T cell receptor (TCR) to interact with its ligand on the gut epithelium. TCR ligation, they suggest, then triggers the secretion of chemokines that draw other damaging cells, such as TNF-producing macrophages, into the gut.