Uneven Colonization of the Lymphoid Periphery by T Cells That Undergo Early TCRα Rearrangements
Uneven Colonization of the Lymphoid Periphery by T Cells That Undergo Early TCRα Rearrangements
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DOI：
10.4049/jimmunol.0804180
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发表时间：
2009-04-01
影响因子：
4.4
通讯作者：
Fink, Pamela J.
中科院分区：
文献类型：
--
作者：
Hendricks, Deborah W.;Fink, Pamela J.
在双阳性阶段之前，少量胸腺细胞在发育早期经历TCR α基因重排。这些细胞对外周血T细胞池的贡献潜力尚不清楚。为了研究外周T细胞区室表达偏向于早期TCR基因重排的库，我们开发了一种小鼠模型，其中TCR α重排仅限于胸腺细胞发育的双阴性阶段。这些小鼠携带floxed RAG 2等位基因和由CD 4启动子驱动的Cre转基因。如所预期的，常规T细胞发育在这样的Cre（+）RAG 2（fl/fl）小鼠中受损，并且发育的TCR α β（+）T细胞在其TCR α库中受到限制，优先使用早期重排的V α基因。在肠道中，Thy-1（+）TCR α β（+）上皮内淋巴细胞（IEL）区室令人惊讶地完整，而Thy-1（-）TCR α β（+）亚群几乎完全不存在。因此，表达作为早期基因重排产物的TCRa库的T细胞可以优先占据不同的IEL区室。尽管有这种能力，但Cre（+）RAG 2（fl/fl）T祖细胞不能与混合骨髓嵌合体中的野生型T祖细胞竞争，这表明在正常小鼠中，经历早期TCR α重排的细胞对外周T细胞池只有很小的贡献。在不存在野生型竞争者的情况下，IEL隔室中的积极的稳态增殖可以促进来自Cre（+）RAG 2（fl/fl）祖细胞的有限群体的相对正常的Thy-1（+）TCR α β（+）T细胞池。免疫学杂志，2009，182：4267-4274.
A sparse population of thymocytes undergoes TCR alpha gene rearrangement early in development, before the double-positive stage. The potential of these cells to contribute to the peripheral T cell pool is unknown. To examine the peripheral T cell compartment expressing a repertoire biased to early TCR gene rearrangements, we developed a mouse model in which TCR alpha rearrangements are restricted to the double-negative stage of thymocyte development. These mice carry floxed RAG2 alleles and a Cre transgene driven by the CD4 promoter. As expected, conventional T cell development is compromised in such Cre(+) RAG2(fl/fl) mice, and the TCR alpha beta(+) T cells that develop are limited in their TCR alpha repertoire, preferentially using early rearranging V alpha genes. In the gut, the Thy-1(+)TCR alpha beta(+) intraepithelial lymphocyte (IEL) compartment is surprisingly intact, whereas the Thy-1(-)TCR alpha beta(+) subset is almost completely absent. Thus, T cells expressing a TCR alpha repertoire that is the product of early gene rearrangements can preferentially populate distinct IEL compartments. Despite this capacity, Cre(+) RAG2(fl/fl) T cell progenitors cannot compete with wild-type T cell progenitors in mixed bone marrow chimeras, suggesting that in normal mice, there is only a small contribution to the peripheral T cell pool by cells that have undergone early TCR alpha rearrangements. In the absence of wild-type competitors, aggressive homeostatic proliferation in the IEL compartment can promote a relatively normal Thy-1(+) TCR alpha beta(+) T cell pool from the limited population derived from Cre(+) RAG2(fl/fl) progenitors. The Journal of Immunology, 2009, 182: 4267-4274.