-transparent.png){kind=logo}
These studies test whether allograft rejection can be blocked by interference with leukocyte adhesion, using a murine IgG2a mAb (R6.5) reactive with monkey ICAM-1 (CD54). In 16 Cynomolgus renal allograft recipients, R6.5 was administered prophylactically as the sole immunosuppressive agent for 12 days (0.01 to 2 mg/kg/day). Survival in 14 recipients with technically successful grafts was significantly prolonged (24.2 +/- 2.4 vs 9.2 +/- 0.6 days for controls; p less than 0.001). Intercellular adhesion molecule-1 (CD54) (ICAM-1) was expressed on vascular endothelium in the kidney and other organs in the monkey in a pattern similar to that in humans. During cellular rejection in controls, ICAM-1 expression increased on endothelial cells, infiltrating mononuclear leukocytes and tubular cells. Biopsies during R6.5 administration showed decreased T cell infiltration (CD2, CD8, CD4) compared with controls and decreased arterial endothelial inflammation. No changes occurred in circulating T cells, aside from variable coating with mIgG. In six of eight other recipients R6.5 administration (0.5 to 2 mg/kg/day for 10 days) reversed preexisting rejection that resulted from taper of Cyclosporine to subtherapeutic levels. Responding grafts showed decreased edema and hemorrhage but no consistent change in the infiltrate. At 1 h after the first dose, mouse IgG deposited primarily on the graft vascular endothelium without any change in the inflammatory infiltrate. Mouse IgG also deposited on the endothelium of normal organs without eliciting an inflammatory response and was cleared from the endothelium within 4 days. Inasmuch as the principal site of binding was the vascular endothelium, we hypothesize that the antibody blocks adhesion to graft ICAM-1 molecules on the vessels. Anti-ICAM-1 also binds to recipient cells and may interfere with Ag presentation and/or T cell interactions. Whatever the mechanism(s), these studies indicate that an anti-ICAM-1 antibody inhibits T cell mediated injury in vivo, and that ICAM-1 is a critical molecule in the pathogenesis of allograft rejection.
A B Cosimi, and
D Conti, and
F L Delmonico, and
F I Preffer, and
S L Wee, and
R Rothlein, and
R Faanes, and
R B Colvin
September 2021,
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons,
A B Cosimi, and
D Conti, and
F L Delmonico, and
F I Preffer, and
S L Wee, and
R Rothlein, and
R Faanes, and
R B Colvin
January 2001,
Journal of biological regulators and homeostatic agents,
A B Cosimi, and
D Conti, and
F L Delmonico, and
F I Preffer, and
S L Wee, and
R Rothlein, and
R Faanes, and
R B Colvin
November 1989,
Transplantation,
A B Cosimi, and
D Conti, and
F L Delmonico, and
F I Preffer, and
S L Wee, and
R Rothlein, and
R Faanes, and
R B Colvin
August 2006,
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons,
A B Cosimi, and
D Conti, and
F L Delmonico, and
F I Preffer, and
S L Wee, and
R Rothlein, and
R Faanes, and
R B Colvin
June 1999,
Nature medicine,
A B Cosimi, and
D Conti, and
F L Delmonico, and
F I Preffer, and
S L Wee, and
R Rothlein, and
R Faanes, and
R B Colvin
November 2001,
Transplantation,
A B Cosimi, and
D Conti, and
F L Delmonico, and
F I Preffer, and
S L Wee, and
R Rothlein, and
R Faanes, and
R B Colvin
February 2017,
The Journal of investigative dermatology,
A B Cosimi, and
D Conti, and
F L Delmonico, and
F I Preffer, and
S L Wee, and
R Rothlein, and
R Faanes, and
R B Colvin
July 1979,
Surgery,
A B Cosimi, and
D Conti, and
F L Delmonico, and
F I Preffer, and
S L Wee, and
R Rothlein, and
R Faanes, and
R B Colvin
February 2024,
Cell reports. Medicine,
A B Cosimi, and
D Conti, and
F L Delmonico, and
F I Preffer, and
S L Wee, and
R Rothlein, and
R Faanes, and
R B Colvin
August 1999,
Clinical immunology (Orlando, Fla.),
