Synergistic effects of combined immunosuppressive modulation. I. Unresponsiveness to dendritic cell-depleted renal allografts in dogs exposed to total-lymphoid irradiation.
Attenuation of the allogeneic stimulus provided by dendritic cells (DC) was achieved by irradiation of the donors, followed by their reconstitution with bone marrow from the prospective DLA-identical recipient. Following long-term (131-187 days) recovery free of graft-versus-host (GVH) disease, the chimeric kidneys were placed into the corresponding recipients; such allografts were rejected at 55, 55, and 60 days, respectively. Four other recipients were conditioned with 1750-1790 cgy of total lymphoid irradiation (TLI) and were then given a similar chimeric kidney from the corresponding partner. These allografts currently survive for 296, 295, 290, and 252 days, respectively. A third group of four dogs was exposed to TLI prior to transplantation of a normal DLA-identical kidney. These grafts were rejected at 20, 42, 46, and 242 days, respectively. Thirteen DLA-identical renal allografts transplanted into normal dogs survived for 13-38 days (mean survival time = 28.6 days). Depletion of allogeneic DC alone, or TLI alone, produced relative prolongations in allograft survival in canine recipients. Combined use of these two modalities, however, resulted in long-term allogeneic unresponsiveness in the recipients.
Rapaport
F T
FT
Department of Surgery, School of Medicine, State University of New York, Stony Brook 11794-8192.
Meek
A
A
Miura
S
S
Hayashi
R
R
Arnold
A N
AN
Strober
S
S
D000818:Animals; D016026:Bone Marrow Transplantation; D002469:Cell Separation; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D004285:Dogs; D005260:Female; D006085:Graft Survival / Q000528:radiation effects; D006649:Histocompatibility Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I; D007108:Immune Tolerance / Q000528:radiation effects; D007165:Immunosuppression Therapy / Q000379:methods*; D016030:Kidney Transplantation; D008297:Male; D011828:Radiation Chimera; D014916:Whole-Body Irradiation
D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; C039692:histocompatibility antigen DLA