Reduced gut intraepithelial lymphocytes in VLA1 null mice

Very late antigen 1 (VLA1) is an integrin collagen receptor that is express ed by lymphocytes in several disease states. VLA1 blockade has been shown t o ameliorate gut disease in experimental graft-versus-host disease. Here we show that in the VLA1 null mouse, which is generally healthy, there is a 5 0% reduction in gut intraepithelial lymphocytes (IELs) despite an otherwise normal lymphocyte distribution in peripheral blood and lymphoid organs. Th e gamma delta to alpha beta ratios of IELs are unchanged. We also find that IL2-stimulated splenocytes from VLA1 null animals show a deficiency in adh esion to fibrillar and basement membrane collagen as well as reduced prolif eration in response to collagen substratum. These results suggest that some , but not all, intraepithelial lymphocytes require VLA1 to survive or proli ferate within the gut epithelium or possibly to traverse the basement membr ane. (C) 2000 Academic Press.