Tolerance induction through simultaneous double bone marrow transplantation with two-signal blockade.
Cotransplantation of donor bone marrow cells (BMCs) in allograft recipients is currently the most promising concept for clinical tolerance induction; however, it still has many difficulties in its successful performance due to the toxicity of the required host conditioning, the risk of engraftment failure, and the problem of graft-versus-host disease (GVHD), as well as the limited accessibility of donor bone marrow cells. Therefore, we performed the studies to determine whether BMCs from multi-donors are simultaneously engrafted and lead to induction of chimerism-based tolerance through the tolerogenic protocol of whom effectiveness we have shown in a previous study. Using a murine model, it was demonstrated that grafted BMCs from BALB/c (H-2(d)) and CBA mice (H-2(k)) establish mixed type and multi-lineage double chimerism and induce immunological donor-specific tolerance to fully MHC-mismatched skin allografts in host C57BL/6 mice (H-2(b)) receiving conditioning with Busulfan and treatment with the two-signal blockade comprised of anti-CD45RB and anti-CD154 monoclonal antibodies.
Lee
Eun-Na
EN
Transplantation Research Center, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangnam-Ku, Seoul 135-710, Republic of Korea.
Lee
Jienny
J
Kim
Eun-Young
EY
Park
Hae-Jung
HJ
Chang
Chi-Young
CY
Jung
Da-Yeon
DY
Choi
Su-Young
SY
Lee
Suk-Koo
SK
Joh
Jae-Won
JW
Kwon
Choon-Hyuck
CH
Noh
Jae-Hyung
JH
Kim
Sung-Joo
SJ
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000379:methods*; D005802:Genes, MHC Class II; D006085:Graft Survival; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016038:Skin Transplantation / Q000276:immunology*; D018183:Transplantation Chimera; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous