Binding of lymphocytes to acutely rejecting rat kidney allografts in vitro is guided by events in the graft itself rather than by sensitization of host lymphocytes.
Circulating host lymphocytes recognize, bind to, become activated by, and infiltrate engrafted allogeneic tissues. The mechanisms responsible for these early events which lead to acute immunological rejection have not been precisely defined. We have examined sequentially in vitro lymphocyte binding patterns in a kidney transplant model of acute rejection in rats and their relationship to the expression of two representative adhesion molecules, ICAM-1 and LFA-1. The extent of binding of naive, or allosensitized recipient strain LNL or PBL, or donor strain or third party cells to frozen sections of kidney allografts was not significantly different; adherence was dependent upon whether the graft was an allograft or an isograft. The pattern of lymphocyte adherence to various allograft compartments was distinct and varied with time. Within 3 days after transplantation only a few cells had bound to the frozen tissues, preferentially to vascular endothelium. By days 5 and 7, increasing numbers of cells bound primarily to tubules, as did the few cells adhering to isografts. Immunohistologically, ICAM-1 expression increased progressively during acute rejection, first on vascular endothelium, later on tubules. LFA-1+ infiltrating cells peaked more quickly. Lymphocyte binding could be inhibited (approx. 40%) by monoclonal antibodies directed against LFA-1 and ICAM-1. The results indicate that in vitro lymphocyte binding to acutely rejecting kidney transplants is directed by the allogenicity of the graft itself via upregulation of adhesion molecules rather than sensitization of the host cells.
Tullius
S G
SG
Surgical Research Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Heemann
U W
UW
Zeilinger
K
K
Azuma
H
H
Tamatami
T
T
Miyasaka
M
M
Tilney
N L
NL
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001667:Binding, Competitive; D002448:Cell Adhesion / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008214:Lymphocytes / Q000276:immunology / Q000502:physiology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1