Graft facilitating cells are derived from hematopoietic stem cells and functionally require CD3, but are distinct from T lymphocytes
Graft facilitating cells are derived from hematopoietic stem cells and functionally require CD3, but are distinct from T lymphocytes
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DOI：
10.1016/j.exphem.2004.07.011
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发表时间：
2004-10-01
影响因子：
2.6
通讯作者：
Ildstad, ST
中科院分区：
文献类型：
--
作者：
Grimes, HL;Schanie, CL;Ildstad, ST
客观的。我们之前证明CD8+/TCR-骨髓细胞有助于HSC在同种异体受体中的植入，而不会引起移植物抗宿主病。促进细胞 (FC) 是否由 T 细胞发育而来或代表不同的谱系尚未确定。方法。在本研究中，我们描述了FC的谱系衍生，定义了CD3复合物在同种异体促进中的作用，并证明了FC而非T细胞的同基因促进。结果。我们首次证明 FC 的发育和功能独立于 T 细胞，并且不能被 T 细胞替代。纯化的 GFP(+) HSC 移植到同基因受体中会产生 GFP(+) FC，这有助于二次移植，证实 FC 源自 HSC。此外，FC（而非 T 细胞）能够有效促进次优数量的 HSC 在同基因受体中的植入。值得注意的是，FC 包含 CD3epsilon 和 CD3delta 的转录本，但不包含 TCRalpha 或 TCRbeta，排除了 T 细胞污染的可能性。导致 CD3 信号传导功能缺陷的基因突变会显着损害同种异体促进中的 FC 功能 (p = 0.006)。结论。综合起来，这些数据清楚地区分了 FC 和 T 细胞。此外，他们表明 FC 需要 CD3epsilon 基因来促进同种异体 HSC 植入。 FC 的独特功能使其成为新的基于细胞的治疗方法的一个有吸引力的焦点，以增强 HSC 植入，同时降低毒性，特别是当可用的 HSC 数量有限时。 (C) 2004 年国际实验血液学学会。由爱思唯尔公司出版
Objective. We previously demonstrated that CD8+/TCR- bone marrow cells facilitate engraftment of HSC in allogeneic recipients without causing graft-vs-host disease. Whether facilitating cells (FC) develop from T cells or represent a distinct lineage has not been determined.Methods. In the present studies, we characterized the lineage derivation of FC, defined the role for the CD3 complex in allogeneic facilitation, and demonstrated syngeneic facilitation by FC but not T cells.Results. We demonstrate for the first time that FC development and function is independent of T cells and cannot be replaced by them. Purified GFP(+) HSC transplanted in syngeneic recipients produce GFP(+) FC, which facilitate in secondary transplants, confirming that FC are derived from HSC. In addition, FC, but not T cells, potently facilitate the engraftment of suboptimal numbers of HSC in syngeneic recipients. Notably, FC contain the transcripts for CD3epsilon and CD3delta, but not TCRalpha or TCRbeta, excluding the possibility of T-cell contamination. Genetic mutations that generate a functional deficiency in CD3 signaling significantly impair FC function in allogeneic facilitation (p = 0.006).Conclusion. Taken together, these data clearly distinguish FC from T cells. Moreover, they indicate that FC require the CD3epsilon gene to facilitate allogeneic HSC engraftment. The unique function(s) of FC make them an attractive focus for new cell-based therapeutic approaches to enhance HSC engraftment while reducing toxicity, especially when limiting numbers of HSC are available. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.