Indefinite islet allograft survival in mice after a short course of treatment with anti-CD45 monoclonal antibodies.
BACKGROUND
Although islet cell transplantation is considered an ideal form of endocrine replacement for type I diabetes, clinical application in humans is still not feasible. New immunosuppressive strategies are clearly needed to control inexorable rejection. CD45 is a family of transmembrane protein tyrosine phosphatases critically involved in the regulation of lymphocyte activation signals. Anti-CD45RB monoclonal antibody can prevent rejection of murine renal allografts.


METHODS
Here, we examine the consequences of targeting CD45 in murine islet cell transplantation. Diabetic mice recipients received islet allografts under the kidney capsule and were divided into seven groups. Recipients received no treatment (controls) or anti-CD45RB monoclonal antibody (mAb; MB23G2 or C363.16A) at different dosages and treatment intervals.


RESULTS
All untreated control animals lost islet function, becoming hyperglycemic within 10-17 days after transplantation. Animals treated with either anti-CD45RB mAb showed a significant prolongation of islet allograft survival when compared with controls. Anti-CD45RB MB23G2 at 100 microg/day, given on days -1, 0, and 5 was particularly effective, inducing indefinite islet allograft survival in 60% of recipients.


CONCLUSIONS
These results indicate that anti-CD45 mAbs are potent immunomodulatory agents, able to sustain indefinite islet allograft function after a short treatment course in the highly immunogenic model of islet transplantation.
Auersvald
L A
LA
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Rothstein
D M
DM
Oliveira
S C
SC
Khuong
C Q
CQ
Onodera
H
H
Lazarovits
A I
AI
Basadonna
G P
GP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D017493:Leukocyte Common Antigens