Allogeneic chimerism established with a mixture of low dose bone marrow cells and splenocytes in sublethally irradiated mice.
BACKGROUND
Allogeneic chimerism has been established in graft-accepting recipients and the donor cells in the host may act in a major way to facilitate the induction of tolerance. In this study, we examined the effects of allogeneic chimerism after injecting donor bone marrow cells (BMCs) mixed with splenocytes (SPLCs) to the sublethally conditioned recipients.


METHODS
In BALB/c(H-2(d)) to B6(H-2(b)) combination, B6 recipients were irradiated at 7.5 Gy and were injected a mixture of donor BMCs and SPLCs intravenously. On day 90 after injection, the degree of chimerism in peripheral blood lymphocytes (PBL) and in the splenocytes was checked by flow cytometry.


RESULTS
In groups which were injected varying BMCs, when > 45 x 10(6) BMCs were injected into B6, a large percentage of donor cells were detected in PBL and in the spleen. In contrast, when < 30 x 10(6) BMCs were injected into B6, only a small percentage of donor cells were detected. In the groups which were injected 3 x 10(6) BMCs with varying SPLCs, when > 10 x 10(6) SPLCs were added, a large percentage of donor cells were detected in PBL and SPLCs, but a small percentage of donor cells were detected with the addition of < 3 x 10(6) SPLCs. A high percentage of chimeric mice showed donor specific tolerance in vitro, mixed lymphocyte responses, and in vivo, skin grafting. In contrast, only a small percentage of chimeric mice showed no donor specific tolerance by skin grafting.


CONCLUSIONS
These findings suggested that even a low dose of BMCs can establish a state of allogeneic chimerism and donor specific tolerance if combined with SPLCs.
Second Department of Surgery, Hirosaki University School of Medicine, Japan. itabashi@cc.hirosaki-u.ac.jp
Yukihiro
Y
Itabashi
Shunji
S
Narumi
Kenichi
K
Hakamada
Nobukazu
N
Watanabe
Kazunori
K
Aoki
Mutsuo
M
Sasaki
D000818:Animals; D016026:Bone Marrow Transplantation; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008815:Mice, Inbred Strains; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000166:cytology*; D018183:Transplantation Chimera / Q000276:immunology*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation