Prolonged survival of rat islet and skin xenografts in mice treated with donor splenocytes and anti-CD154 monoclonal antibody.
Treatment of C57BL/6 mice with one transfusion of BALB/c spleen cells and a brief course of anti-CD154 (anti-CD40 ligand) antibody permits BALB/c islet grafts to survive indefinitely and BALB/c skin grafts to survive for approximately 50 days without further intervention. We now report adaptation of this protocol to the transplantation of islet and skin xenografts. We observed prolonged survival of rat islet xenografts in mice treated with donor-specific spleen cell transfusion and anti-CD154 monoclonal antibody (mAb). Challenge islet xenografts placed on these animals indicated that graft acceptance was species-specific but not strain specific. Spleen cells from recipients bearing intact grafts led to rejection of rat islet xenografts in scid mice, suggesting that graft acceptance was not due to complete clonal deletion of xenoreactive cells. We also observed prolonged survival of rat skin xenografts in mice treated with donor-specific transfusion and anti-CD154 mAb. Prolonged survival of skin xenografts was also species specific. We conclude that treatment with appropriately timed donor-specific transfusion and anti-CD154 mAb induces durable survival of both islet and skin xenografts in mice. Because this procedure is targeted directly at CD154, a co-activation molecule expressed predominantly by activated CD4+ T-cells, the results suggest that CD4+ cells have a major role in the cellular immune response to xenografts.
Department of Medicine, University of Massachusetts Medical School, Worcester, USA.
E J
EJ
Gordon
T G
TG
Markees
N E
NE
Phillips
R J
RJ
Noelle
L D
LD
Shultz
J P
JP
Mordes
A A
AA
Rossini
D L
DL
Greiner
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D023201:CD40 Ligand; D017690:Cell Transplantation; D006085:Graft Survival / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D051381:Rats; D011919:Rats, Inbred Strains; D016038:Skin Transplantation; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D014019:Tissue Donors; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D023201:CD40 Ligand