Adoptive immunotherapy against kidney targets in dog-leukocyte antigen-identical mixed hematopoietic canine chimeras.
BACKGROUND
Stable mixed-donor-host-hematopoietic chimerism can serve as a platform for adoptive immunotherapy. Infusions of donor lymphocytes (DLI) sensitized against hematopoietic cells converted mixed hematopoietic into full-donor chimerism in dog-leukocyte antigen (DLA)-identical littermates. Whether sensitization against tissue of solid organs leads to organ-specific immunity that can be transferred by DLI was unknown and was investigated in these experiments using the kidney as target.


METHODS
DLA-identical recipients with established stable mixed-donor-host-hematopoietic chimerism were used. In five pairs, hematopoietic stem-cell transplant (HSCT) donors were sensitized by kidney transplantation from the respective chimeras. In a second group, five HSCT donors received vaccinations that were generated from kidney cells of the respective mixed chimeras. Twenty-eight days after sensitization, DLI were administered to the mixed-hematopoietic chimeras.


RESULTS
All HSCT donors rejected their kidney grafts from their mixed-chimeric recipients within 22 to 45 days. DLI caused no sustained graft-versus-kidney effects in the mixed-chimeric recipients. However, DLI donors sensitized by kidney transplantation converted 4 of 5 mixed chimeras into virtually complete (>95%) donor-type chimeras, compared with 1 of 5 mixed chimeras given DLI by vaccination from sensitized donors.


CONCLUSIONS
Although DLA-identical kidney grafts from mixed-hematopoietic chimeras were readily rejected by their HSCT donors, subsequent transfusions of sensitized-donor lymphocytes into mixed chimeras converted mixed to all-donor chimerism but failed to induce graft-versus-kidney effects. Vaccination strategies in lieu of kidney grafts failed to convert mixed chimerism.
Junghanss
Christian
C
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Takatu
Alessandra
A
Little
Marie-Terese
MT
Maciej Zaucha
J
J
Zellmer
Eustacia
E
Yunusov
Murad
M
Sale
George
G
Georges
George E
GE
Storb
Rainer
R
D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004285:Dogs; D005260:Female; D006084:Graft Rejection / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D006086:Graft vs Host Disease / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D016219:Immunotherapy, Adoptive; D066298:In Vitro Techniques; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D018183:Transplantation Chimera / Q000276:immunology*; D014463:Ultrasonography; D014612:Vaccines / Q000494:pharmacology
D006680:HLA Antigens; D014612:Vaccines; D003404:Creatinine