Reduced gut intraepithelial lymphocytes in VLA1 null mice.
Very late antigen 1 (VLA1) is an integrin collagen receptor that is expressed by lymphocytes in several disease states. VLA1 blockade has been shown to 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 50% reduction in gut intraepithelial lymphocytes (IELs) despite an otherwise normal lymphocyte distribution in peripheral blood and lymphoid organs. The gammadelta to alphabeta ratios of IELs are unchanged. We also find that IL2-stimulated splenocytes from VLA1 null animals show a deficiency in adhesion to fibrillar and basement membrane collagen as well as reduced proliferation in response to collagen substratum. These results suggest that some, but not all, intraepithelial lymphocytes require VLA1 to survive or proliferate within the gut epithelium or possibly to traverse the basement membrane.
Meharra
E J
EJ
Department of Cell Biology, The Scripps Research Institute, La Jolla, California, 92037, USA.
Schön
M
M
Hassett
D
D
Parker
C
C
Havran
W
W
Gardner
H
H
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D039222:Integrin alpha1beta1; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology*; D007583:Jejunum / Q000166:cytology; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D038981:Receptors, Collagen; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
D039222:Integrin alpha1beta1; D016023:Integrins; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D038981:Receptors, Collagen; D003094:Collagen