Maeda Yoshinobu, Tawara Isao, Teshima Takanori, Liu Chen, Hashimoto Daigo, Matsuoka Ken-Ichi, Tanimoto Mitsune, Reddy Pavan
Department of Medicine, Okayama University, Okayama, Japan.
Exp Hematol. 2007 Feb;35(2):274-86. doi: 10.1016/j.exphem.2006.10.010.
T cells that undergo lymphopenia-induced proliferation (LIP) are characterized by greater effector and anti-tumor function than naïve T cells. But the ability of these T cells in causing graft-versus-host disease (GVHD) is not known.
We tested the hypothesis that donor T cells that had undergone LIP would cause more severe GVHD than naïve T cells by utilizing well-characterized murine experimental models of allogeneic bone marrow transplantation (BMT).
Contrary to our hypothesis, LIP of donor T cells under either noninflammatory or irradiated conditions caused significantly reduced GVHD as determined by survival, clinical, pathologic, and biochemical parameters than naïve T cells. Compared to naïve donor T cells, LIP T cells demonstrated reduced expansion in vivo and in vitro after allogeneic BMT. The reduction in GVHD mortality and severity was observed across multiple strains after allogeneic BMT. In vivo mechanistic studies by cell depletion demonstrated an increase in the CD44(hi) "memory" phenotype T cells and not the CD4(+)CD25(+) T cell subset to be critical for the reduction in GVHD.
These data demonstrate that LIP of T cells regulates acute GVHD severity in contrast to their ability to cause increased allograft rejection, autoimmunity, or anti-tumor immunity.
经历淋巴细胞减少诱导增殖（LIP）的T细胞，其效应和抗肿瘤功能比初始T细胞更强。但这些T细胞引发移植物抗宿主病（GVHD）的能力尚不清楚。
我们利用特征明确的同种异体骨髓移植（BMT）小鼠实验模型，检验经历LIP的供体T细胞比初始T细胞引发更严重GVHD这一假设。
与我们的假设相反，在非炎症或辐照条件下，供体T细胞的LIP导致的GVHD在生存、临床、病理和生化参数方面均比初始T细胞显著减轻。与初始供体T细胞相比，LIP T细胞在同种异体BMT后体内和体外的扩增均减少。同种异体BMT后在多个品系中均观察到GVHD死亡率和严重程度降低。通过细胞清除进行的体内机制研究表明，对于GVHD的减轻，关键在于CD44(hi) “记忆”表型T细胞增加，而非CD4(+)CD25(+) T细胞亚群。
这些数据表明，T细胞的LIP与它们引发同种异体移植排斥、自身免疫或抗肿瘤免疫增加的能力相反，可调节急性GVHD的严重程度。
