Effect of locally administered anti-CD154 (CD40 ligand) monoclonal antibody on survival of allogeneic corneal transplants.
OBJECTIVE
To determine the effect of ocular administration of anti-CD154 monoclonal antibody on the survival of orthotopic murine corneal transplants.


METHODS
BALB/c mice were used as recipients of multiple minor H- and MHC-mismatched orthotopic corneal transplants. Recipient beds were either avascular (normal-risk) or neovascularized (high-risk) at the time of surgery. Mice were randomized to receive either anti-CD154 antibody or control immunoglobulin by subconjunctival injection. All grafts were evaluated for signs of rejection by slitlamp biomicroscopy until week 20-24 with the therapy tapered and discontinued after week 8 and week 12, respectively.


RESULTS
In normal-risk transplantation, the 8-week survival rate improved from 30% in control mice to 90% in anti-CD154 treated mice (p= 0.0061). In high-risk transplantation, the survival rate of anti-CD154-treated mice was enhanced to 55% compared with 0% in control mice at week 8 (p= 0.0184); however, tapering and termination of anti-CD154 led to some loss in graft survival, with a survival rate of 56% in normal-risk recipients, and 22% in high-risk recipients by week 20. Anti-CD40L treated animals displayed lower grades of postoperative corneal neovascularization (p<0.05), in particular in normal-risk recipients.


CONCLUSIONS
Local ocular administration of anti-CD154 is effective in the prevention of corneal allograft rejection in normal-risk recipients, and in delaying the incidence of rejection in high-risk recipients. Long-term graft survival may not be fully achieved following termination of the CD40-CD154 pathway blockade.
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, U.S.A.
Ying
Y
Qian
M Reza
MR
Dana
D000287:Administration, Topical; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D003315:Cornea / Q000276:immunology; D016510:Corneal Neovascularization / Q000473:pathology; D016039:Corneal Transplantation / Q000473:pathology / Q000502:physiology*; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D023201:CD40 Ligand