Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine

The alpha 4 beta 7 integrin plays a central role in the homing of T cells to the gut. We hypothesized that absence of the beta 7 subunit would result in a reduction of intestinal graft-versus-host disease (GVHD) and an improvement in overall GVHD morbidity and mortality in recipients of hematopoietic stem cell transplantation (HSCT). Analysis of alloreactive beta 7(-/-) T cells showed intact activation, proliferation, cytolkine production, and cytotoxicity. However, recipients of beta 7(-/-) donor T cells in murine HSCT models experienced less GVHD morbidity and mortality than recipients of wild-type (WT) T cells, associated with a decrease in donor T-cell infiltration of the liver and intestine and with an overall significant decrease in hepatic and intestinal GVHD. In graft-versus-tumor (GVT) experiments, we demonstrated intact or even enhanced GVT activity of beta 7(-/-) donor T cells. In conclusion, beta 7(-/-) donor T cells caused less GVHD morbidity and mortality than WT donor T cells because of selectively decreased T-cell infiltration of the liver and intestines. Our data suggest that strategies to target the beta 7 integrin have the clinical potential to alleviate or prevent GVHD while sparing or potentiating GVT activity.