Anti-CD3 treatment facilitates engraftment of full H-2-disparate donor bone marrow cells and subsequent skin allograft tolerance.
The aim of the present study was to induce engraftment of full H-2-disparate donor bone marrow cells and the development of subsequent transplantation tolerance. To this end, recipient H-2b mice were treated with anti-CD3 and on the same day received 6 Gy whole body irradiation as well as donor bone marrow cells (H-2d). Anti-CD3 treatment was chosen because it results in suppression of T cell function and in the release of CSF associated with enhancement of donor bone marrow engraftment. Stable, long-term chimerism measured in peripheral blood and mesenteric lymph nodes was obtained using this preparative regimen. In contrast, the use of anti-CD3 F(ab')2 fragments failed to induce donor bone marrow cell engraftment, suggesting indeed an important role of anti-CD3-mediated growth factor production in marrow engraftment. To overcome the side effects of anti-CD3 treatment (cytokine release syndrome), anti-CD4 was given 1 day before the treatment protocol. Omission of anti-CD3 resulted in failure of donor bone marrow engraftment, indicating the essential role of anti-CD3 treatment in marrow engraftment. Skin transplantation performed 2 and 6 months after this well-tolerated conditioning regimen showed indefinite survival of first and second grafts, respectively. In addition, specific CTL nonresponsiveness developed, demonstrating the presence of classical transplantation tolerance across a full H-2 barrier.
de Vries-van Der Zwan
A
A
Department of Transplantation Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Besseling
A C
AC
Kievits
F
F
van Twuyver
E
E
de Waal
L P
LP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002678:Chimera / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D000939:Epitopes; D005260:Female; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology* / Q000528:radiation effects; D006183:H-2 Antigens / Q000276:immunology*; D007128:Immunoglobulin Fragments / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology*; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D000939:Epitopes; D006183:H-2 Antigens; D007128:Immunoglobulin Fragments; D007166:Immunosuppressive Agents