A CD200FC immunoadhesin prolongs rat islet xenograft survival in mice.
BACKGROUND
A solubilized form of the CD200 molecule, CD200Fc, has been shown to suppress allograft rejection and development of collagen-induced arthritis in mice. We investigated whether the same molecule could prolong survival of rat islet xenografts.


METHODS
Streptozocin-treated mice, receiving injections with anti-asialo-GM1 antibody, received rat islets ( approximately 400/mouse) under the kidney capsule or injected into the portal vein, along with rapamycin treatment. Thereafter mice received injections of CD200Fc (10 microg/mouse/injection) or control mouse IgG2. Blood glucose was monitored daily. Some mice received additional injections of anti-CD200/-CD200R monoclonal antibodies.


RESULTS
Portal vein delivery of islets led to more extended resolution of diabetes than did transplantation under the kidney capsule. CD200Fc further prolonged survival in either case, an effect abolished by anti-CD200 or F(ab')2 anti-CD200R mAbs, but not by whole anti-CD200R (anti-CD200R Ig). Spleen cells taken from CD200Fc-treated mice showed polarization to type-2 cytokine production (interleukin-4, interleukin-10) on restimulation with rat splenocytes in culture, in comparison to cells from control mice (type-1 cytokines, interlulin-2, interferon-gamma).


CONCLUSIONS
CD200:CD200R interactions are important in regulating rat islet xenograft survival.
The Toronto Hospital, University Health Network and Department of Surgery, University of Toronto, Toronto, Canada M5G2C4.
R M
RM
Gorczynski
J
J
Hu
Z
Z
Chen
Y
Y
Kai
J
J
Lei
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D000954:Antigens, Surface / Q000276:immunology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D006085:Graft Survival; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011917:Rats, Inbred Lew; D013311:Streptozocin; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D001786:Blood Glucose; D016207:Cytokines; D013311:Streptozocin; C042739:antigens, CD200