Kanamoto Akira, Maki Takashi
Transplant Center, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
J Immunol. 2004 Feb 1;172(3):1444-8. doi: 10.4049/jimmunol.172.3.1444.
Donor hemopoietic cell engraftment is considered to be an indicator of allograft tolerance. We depleted chimerism with cells specifically presensitized to the bone marrow donor to investigate its role in mixed chimera-induced tolerance. Three experimental models were used: model A, B10.A cells presensitized to B6 (a anti-b cells) were injected into (B6 x D2)F(1) --> B10.A mixed chimeras grafted with DBA/2 skin; model B, anti-B6 presensitized cells prepared in DBA/2 --> B10.A mixed chimeras, thus unresponsive to DBA/2 (a anti-b/tol-d cells), were injected into (B6 x D2)F(1) --> B10.A mixed chimeras grafted with DBA/2 skin; and model C, (BALB/c x B6)F(1) cells presensitized to CBA (d/b anti-k cells) were injected into (B6 x CBA)F(1) --> BALB/c mixed chimeras grafted with B6 skin. Skin was grafted on day 30. Injection of each cell type before skin grafting abolished hemopoietic cell engraftment and prevented allograft acceptance. Injection of presensitized cells after skin grafting resulted in different outcomes depending on the models. In model A, injection of a anti-b cells completely depleted chimerism and caused allograft rejection. In model B, injection of a anti-b/tol-d cells markedly reduced, but did not deplete, peripheral chimerism and maintained skin allograft survival. In model C, d/b anti-k cells reduced chimerism to the background levels but failed to cause graft rejection, probably due to persistence of injected cells which share MHC with skin grafts. Together, the results show that presence of chimeric donor cells is essential in both the induction and maintenance phases of tolerance induced by mixed chimerism.
供体造血细胞植入被认为是同种异体移植耐受的一个指标。我们用对骨髓供体具有特异性预致敏的细胞清除嵌合状态，以研究其在混合嵌合体诱导的耐受中的作用。使用了三种实验模型：模型A，将对B6（a抗b细胞）预致敏的B10.A细胞注入（B6×D2）F1→B10.A混合嵌合体并移植DBA/2皮肤；模型B，将在DBA/2中制备的抗B6预致敏细胞注入B10.A混合嵌合体，使其对DBA/2（a抗b/tol-d细胞）无反应，然后将这些细胞注入（B6×D2）F1→B10.A混合嵌合体并移植DBA/2皮肤；模型C，将对CBA（d/b抗k细胞）预致敏的（BALB/c×B6）F1细胞注入（B6×CBA）F1→BALB/c混合嵌合体并移植B6皮肤。在第30天进行皮肤移植。在皮肤移植前注射每种细胞类型都会消除造血细胞植入并阻止同种异体移植的接受。在皮肤移植后注射预致敏细胞根据模型不同产生了不同的结果。在模型A中，注射a抗b细胞完全清除了嵌合状态并导致同种异体移植排斥。在模型B中，注射a抗b/tol-d细胞显著降低但未清除外周嵌合状态，并维持了皮肤同种异体移植的存活。在模型C中，d/b抗k细胞将嵌合状态降低到背景水平，但未能导致移植排斥，这可能是由于注射的细胞与皮肤移植物共享MHC而持续存在。总之，结果表明嵌合供体细胞的存在在混合嵌合体诱导的耐受的诱导和维持阶段都是必不可少的。
