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表达不同T细胞抗原受体的胸腺细胞按发育顺序出现。

Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors.

作者信息

Havran W L, Allison J P

机构信息

Cancer Research Laboratory, University of California, Berkeley 94720.

出版信息

Nature. 1988 Sep 29;335(6189):443-5. doi: 10.1038/335443a0.

Abstract

The T-cell repertoire is elaborated by a still poorly understood process during which precursor cells arising in the bone marrow seed the thymus to provide a starting point for intrathymic differentiation and selection. The products of the process are cells which express antigen receptors composed of either alpha/beta or gamma/delta heterodimers in association with CD3. The finding that the appearance of T-cell antigen receptor gamma- and delta-gene rearrangements and transcripts precedes those of full-length beta- and alpha-transcripts during ontogeny indicates that the process is ordered, a conclusion supported by the fact that the appearance of thymocytes expressing CD3-associated gamma/delta heterodimers precedes the appearance of those bearing alpha/beta heterodimers. The recent demonstrations that within the gamma- and delta-loci there is ordered and sometimes transient rearrangement and expression of specific V delta and V gamma gene segments during ontogeny raised the possibility that qualitative changes in the capacity of the differentiative process to generate components of the T-cell armamentarium might occur. We have produced a monoclonal antibody that detects an epitope of the V gamma 3 gene product, a gene segment expressed only in the early fetal thymus. In this report we demonstrate that cells expressing V gamma 3 are present transiently at the earliest stages of thymocyte development, preceding the appearance of cells bearing other gamma/delta or alpha/beta receptors. In the adult mouse, V gamma 3 expression appears to be limited to Thy-1+ cells in the epidermis. These results suggest a profound programming and staging in elaboration of the components of the T-cell system during the early stages of thymocyte development in the embryo.

摘要

T细胞库是通过一个仍未被充分理解的过程形成的,在此过程中,骨髓中产生的前体细胞定植于胸腺,为胸腺内的分化和选择提供起点。该过程的产物是表达由α/β或γ/δ异二聚体与CD3结合组成的抗原受体的细胞。在个体发育过程中,T细胞抗原受体γ和δ基因重排及转录本的出现先于全长β和α转录本,这一发现表明该过程是有序的,胸腺细胞表达与CD3相关的γ/δ异二聚体先于表达α/β异二聚体的胸腺细胞出现这一事实也支持了这一结论。最近的研究表明,在个体发育过程中,γ和δ基因座内特定的Vδ和Vγ基因片段存在有序且有时是短暂的重排和表达,这增加了分化过程产生T细胞武器库成分的能力可能发生质的变化的可能性。我们制备了一种单克隆抗体,它能检测Vγ3基因产物的一个表位,该基因片段仅在胎儿早期胸腺中表达。在本报告中,我们证明表达Vγ3的细胞在胸腺细胞发育的最早阶段短暂存在,先于表达其他γ/δ或α/β受体的细胞出现。在成年小鼠中,Vγ3的表达似乎仅限于表皮中的Thy-1+细胞。这些结果表明,在胚胎胸腺细胞发育的早期阶段,T细胞系统成分的形成存在深刻的编程和阶段划分。

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