Lineage diversion of T cell receptor transgenic thymocytes revealed by lineage fate mapping.

Lineage diversion of T cell receptor transgenic thymocytes revealed by lineage fate mapping.
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DOI:
10.1371/journal.pone.0001512
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发表时间:
2008-01-30
期刊:
影响因子:
3.7
通讯作者:
von Boehmer H
von Boehmer H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Egawa T;Kreslavsky T;Littman DR;von Boehmer H

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胸腺中T细胞受体(TCR)与主要组织相容性复合体(MHC)分子的结合决定了TCRαβ淋巴细胞的命运,后者随后归巢至次级淋巴组织。TCR转基因模型已用于研究胸腺选择和谱系定型。大多数TCR转基因小鼠在双阴性阶段过早表达重排的TCRαβ,并且在TCR转基因小鼠的次级淋巴组织中发现了在非转基因小鼠中不易检测到的异常T细胞TCRαβ群体。为了确定TCR转基因胸腺细胞的发育途径,我们使用了Cre-LoxP介导的命运作图,并在此显示转基因TCRαβ的过早表达使一些发育中的胸腺细胞转向类似于γ δ细胞的发育途径。我们发现,雄性小鼠中大多数具有HY-TCR的外周T细胞绕过RORγ t阳性CD 4 +8+(双阳性,DP)阶段,以CD 4 −8−(双阴性,DN)或CD 8 α+ T细胞的形式在淋巴结或肠道上皮中积累。同样,雌性小鼠淋巴组织中的DN TCRαβ细胞并非源自DP胸腺细胞。结果进一步支持了TCRαβ的过早表达可使DN胸腺细胞转向γ δ谱系细胞的假设。
The binding of the T cell receptor (TCR) to major histocompatibility complex (MHC) molecules in the thymus determines fates of TCRαβ lymphocytes that subsequently home to secondary lymphoid tissue. TCR transgenic models have been used to study thymic selection and lineage commitment. Most TCR transgenic mice express the rearranged TCRαβ prematurely at the double negative stage and abnormal TCRαβ populations of T cells that are not easily detected in non-transgenic mice have been found in secondary lymphoid tissue of TCR transgenic mice. To determine developmental pathways of TCR-transgenic thymocytes, we used Cre-LoxP-mediated fate mapping and show here that premature expression of a transgenic TCRαβ diverts some developing thymocytes to a developmental pathway which resembles that of gamma delta cells. We found that most peripheral T cells with the HY-TCR in male mice have bypassed the RORγt-positive CD4+8+ (double positive, DP) stage to accumulate either as CD4−8− (double negative, DN) or as CD8α+ T cells in lymph nodes or gut epithelium. Likewise, DN TCRαβ cells in lymphoid tissue of female mice were not derived from DP thymocytes. The results further support the hypothesis that the premature expression of the TCRαβ can divert DN thymocytes into gamma delta lineage cells.
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