Lu L, Rudert W A, Qian S, McCaslin D, Fu F, Rao A S, Trucco M, Fung J J, Starzl T E, Thomson A W
Pittsburgh Transplantation Institute, University of Pittsburgh, Pennsylvania 15213, USA.
J Exp Med. 1995 Aug 1;182(2):379-87. doi: 10.1084/jem.182.2.379.
Allografts of the liver, which has a comparatively heavy leukocyte content compared with other vascularized organs, are accepted permanently across major histocompatibility complex barriers in many murine strain combinations without immunosuppressive therapy. It has been postulated that this inherent tolerogenicity of the liver may be a consequence of the migration and perpetuation within host lymphoid tissues of potentially tolerogenic donor-derived ("chimeric") leukocytes, in particular, the precursors of chimeric dendritic cells (DC). In this study, we have used granulocyte/macrophage colony-stimulating factor to induce the propagation of progenitors that give rise to DC (CD45+, CD11c+, 33D1+, nonlymphoid dendritic cell 145+, major histocompatibility complex class II+, B7-1+) in liquid cultures of murine bone marrow cells. Using this technique, together with immunocytochemical and molecular methods, we show that, in addition to cells expressing female host (C3H) phenotype (H-2Kk+; I-E+; Y chromosome-), a minor population of male donor (B10)-derived cells (H-2Kb+; I-A+; Y chromosome+) can also be grown in 10-d DC cultures from the bone marrow of liver allograft recipients 14 d after transplant. Highly purified nonlymphoid dendritic cell 145+ DC sorted from these bone marrow-derived cell cultures were shown to comprise approximately 1-10% cells of donor origin (Y chromosome+) by polymerase chain reaction analysis. In addition, sorted DC stimulated naive, recipient strain T lymphocytes in primary mixed leukocyte cultures. Evidence was also obtained for the growth of donor-derived cells from the spleen but not the thymus. In contrast, donor cells could not be propagated from the bone marrow or other lymphoid tissues of nonimmunosuppressed C3H mice rejecting cardiac allografts from the same donor strain (B10). These findings provide a basis for the establishment and perpetuation of cell chimerism after organ transplantation.
与其他血管化器官相比，肝脏的同种异体移植物含有相对较多的白细胞，在许多小鼠品系组合中，无需免疫抑制治疗即可永久性地跨越主要组织相容性复合体屏障被接受。据推测，肝脏这种固有的致耐受性可能是潜在的致耐受性供体来源（“嵌合”）白细胞，特别是嵌合树突状细胞（DC）前体在宿主淋巴组织内迁移和持续存在的结果。在本研究中，我们使用粒细胞/巨噬细胞集落刺激因子诱导在小鼠骨髓细胞的液体培养物中产生DC（CD45 +、CD11c +、33D1 +、非淋巴样树突状细胞145 +、主要组织相容性复合体II类 +、B7 - 1 +）的祖细胞增殖。使用该技术，结合免疫细胞化学和分子方法，我们发现，除了表达雌性宿主（C3H）表型（H - 2Kk +；I - E +；Y染色体 -）的细胞外，一小部分雄性供体（B10）来源的细胞（H - 2Kb +；I - A +；Y染色体 +）也可以在移植后14天从肝脏同种异体移植受体的骨髓中进行10天的DC培养。通过聚合酶链反应分析显示，从这些骨髓来源的细胞培养物中高度纯化的非淋巴样树突状细胞145 + DC包含约1 - 10%的供体来源（Y染色体 +）细胞。此外，分选的DC在原发性混合白细胞培养物中刺激幼稚的受体品系T淋巴细胞。还获得了供体来源细胞在脾脏而非胸腺中生长的证据。相比之下，在排斥来自同一供体品系（B10）心脏同种异体移植物的未免疫抑制的C3H小鼠的骨髓或其他淋巴组织中，供体细胞无法增殖。这些发现为器官移植后细胞嵌合的建立和持续存在提供了基础。
