Most IL-4-producing γδ thymocytes of adult mice originate from fetal precursors
Most IL-4-producing γδ thymocytes of adult mice originate from fetal precursors
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DOI：
10.4049/jimmunol.171.5.2413
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发表时间：
2003-09-01
影响因子：
4.4
通讯作者：
Pereira, P
中科院分区：
文献类型：
--
作者：
Grigoriadou, K;Boucontet, L;Pereira, P
y-1（暗淡）γ - δ T细胞构成了一个独特的成年γ - δ T细胞亚群，其特征是表达由vgamma1 - gamma4和Vdelta6Cdelta链组成的TCR，其连接序列多样性有限。然而，表达Thy-1（暗）tcr - γ - δ基因的几个特征，特别是N区多样性的缺失或极少存在以及几乎不变的Ddelta2-Jdelta1连接，是胎儿胸腺中常见的重排的典型特征。在这项研究中，我们研究了这些细胞的起源。无论受体小鼠是否被给予成人骨髓或胎儿肝细胞作为造血前体来源，在同基因辐射成体嵌合体中很少有Thy-1（沉闷）γ - δ胸腺细胞发育。相比之下，移植到成人同基因受体的胎儿胸腺中Thy-1（暗淡）γ δ T细胞数量正常。有趣的是，移植物中存在的大多数Thy-1（暗）γ -胸腺细胞来自移植物，即使移植物胸腺中的大多数常规γ -和α -胸腺细胞来自受体来源的T细胞前体。对成年Thy-1（沉闷）γ δ胸腺细胞中存在的非选择性tcr - γ重排的单细胞PCR分析显示，这些细胞中有一半以上是有限数量的克隆的后代，这些克隆可能在生命的最初几周内大大扩展。最后，大量Thy-1（迟钝）γ δ T细胞的第二个TCR-delta等位基因包含不完全的TCR-delta重排，从而解释了之前在Thy-1（迟钝）γ δ胸腺细胞中发现的无功能V(D)J重排中的成体型重排。
Thy-1(dull) gammadelta T cells constitute a distinct adult gammadelta T cell subset characterized by the expression of a TCR composed of Vgamma1Cgamma4 and Vdelta6Cdelta chains with limited junctional sequence diversity. However, several features of the expressed Thy-1(dull) TCR-gammadelta genes, in particular the absence or minimal presence of N region diversity and the almost invariable Ddelta2-Jdelta1 junction, are typical of rearrangements often found in the fetal thymus. In this study, we have investigated the origin of these cells. Few Thy-1(dull) gammadelta thymocytes developed in syngeneic radiation adult chimeras, regardless of whether the recipient mice were given adult bone marrow or fetal liver cells as a source of hemopoietic precursors. In contrast, normal numbers of Thy-1(dull) gammadelta T cells developed in fetal thymi grafted into adult syngeneic recipients. Interestingly, the majority of Thy-1(dull) gammadelta thymocytes present in the grafts were of graft origin, even when most conventional gammadelta and alphabeta thymocytes in the grafted thymi originated from T cell precursors of recipient origin. Single-cell PCR analyses of the nonselected TCR-gamma rearrangements present in adult Thy-1(dull) gammadelta thymocytes revealed that more than one-half of these cells represent the progenies of a limited number of clones that greatly expanded possibly during the first weeks of life. Finally, the second TCR-delta allele of a large number of Thy-1(dull) gammadelta T cells contained incomplete TCR-delta rearrangements, thus providing an explanation for the adult-type rearrangements previously found among nonfunctional V(D)J rearrangements present in Thy-1(dull) gammadelta thymocytes.