IL-7-dependent homeostatic proliferation in the presence of a large number of T cells in gld mice
IL-7-dependent homeostatic proliferation in the presence of a large number of T cells in gld mice
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DOI：
10.1111/j.1348-0421.2004.tb03539.x
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发表时间：
2004-01-01
影响因子：
2.6
通讯作者：
Onoé, K
中科院分区：
文献类型：
--
作者：
Aranami, T;Iclozan, C;Onoé, K
在gld小鼠中，CD 4和8双阴性（DN）T细胞以及幼稚和记忆表型T细胞在外周淋巴器官中积累。尽管Fas配体（L）缺陷解释了异常DN T细胞的进行性积累，但在gld小鼠中可能涉及缺陷性稳态的其他机制的存在尚不清楚。在这项研究中，我们分析了T细胞稳态在gld小鼠采用过继转移系统。显示gld而不是C57 BL/6（136）环境导致转移的B6 T细胞的增殖增强而不上调CD 69。因此，增强的T细胞增殖似乎是由异常稳态增殖引起的，即使在大量受体T细胞存在的情况下。来自lpr小鼠的T细胞在B6环境中没有显示出显著的增殖，这表明Fas-Fas L相互作用的缺乏不是导致异常稳态增殖的原因。虽然在gld和B6小鼠脾脏中检测到相似的IL-7 mRNA水平，但gld小鼠T细胞中CD 127的强度和CD 127（+）细胞的比例显著低于B6小鼠，表明在gld环境中IL-7过量是导致转移的T细胞异常增殖的原因。给予抗CD 127抗体可抑制转移淋巴细胞的增殖。因此，IL-7依赖性增殖似乎参与了gld受体中淋巴细胞的异常增殖。
In gld mice, CD4 and 8-double-negative (DN) T cells as well as naive and memory-phenotype T cells accumulate in the peripheral lymphoid organs. Although Fas ligand (L) defect accounts for the progressive accumulation of abnormal DN T cells, the existence of other mechanisms which may be involved in the defective homeostasis in gld mice has been unclear. In this study, we analyze T-cell homeostasis in gld mice using adoptive transfer systems. It was shown that a gld, but not C57BL/6 (136), environment led to augmented proliferation of B6 T cells transferred without up-regulation of CD69. Thus, the augmented T-cell proliferation seemed to result from mal-homeostatic proliferation even in the presence of a large number of recipient T cells. T cells from lpr mice showed no significant proliferation in the B6 environment, suggesting that the absence of Fas-Fas L interaction was not responsible for the mal-homeostatic proliferation. Although similar levels of IL-7 mRNA were detected in gld and B6 spleens, the intensity of CD127 and the proportion of CD127(+) cells in the T cells were significantly lower in gld mice than in B6 mice, suggesting that IL-7 excess in a gld environment is responsible for the abnormal proliferation of transferred T cells. The administration of anti-CD127 antibody inhibited the proliferation of transferred lymphocytes. Thus, IL-7-dependent proliferation seems to be involved in the abnormal proliferation of lymphocytes in gld recipients.