Thymic selection and cell division.
Thymic selection and cell division.
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DOI：
10.1084/jem.182.4.961
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发表时间：
1995-10-01
期刊：
影响因子：
--
通讯作者：
Sprent J
中科院分区：
文献类型：
--
作者：
Ernst B;Surh CD;Sprent J
使用一个系统研究胸腺选择过程中的细胞分裂，其中纯化的 T 细胞抗原受体 (TCR)-CD4+8+（双阳性 [DP]）细胞群和胎儿胸腺上皮细胞 (TEC) 在组织培养中重新聚集。在该系统中，未成熟的 DP 细胞在 3-4 天内分化为成熟的单阳性 (SP) CD4+8- 和 CD4-8+ TCRhi 细胞，表明正选择。通过向培养物中添加 DNA 前体溴脱氧尿苷并对细胞进行染色以进行溴脱氧尿苷掺入，发现重新聚集培养物中的 T 细胞分裂在第 1 天较高，在第 2 天较低，在第 4-5 天较高。细胞分离研究表明，第一天的细胞分裂仅限于 DP 母细胞。在没有母细胞的情况下，小DP细胞无法增殖并分化为SP细胞而没有细胞分裂，因此表明增殖不是正选择的重要组成部分。这适用于前 2-3 天内产生的 SP 细胞。令人惊讶的是，培养后期产生的 SP 细胞显示出很高的细胞分裂率；增殖的SP细胞是TCRhi并且包括CD4+8-和CD4-8+细胞。 TCRhi SP 细胞的更新在正常新生儿胸腺和用成人淋巴结 T 细胞制备的 TEC 重新聚集培养物中也很显着。我们推测围产期胸腺微环境中成熟 SP 细胞的分裂是由 TEC 释放的刺激性细胞因子驱动的。这种增殖可能是在输出到外周之前扩展成熟 T 细胞库的一种手段。
Cell division during thymic selection was studied with a system in which purified populations of T cell antigen receptor (TCR)- CD4+8+ (double-positive [DP]) cells and fetal thymic epithelial cells (TEC) were reaggregated in tissue culture. In this system, immature DP cells differentiate into mature single-positive (SP) CD4+8- and CD4-8+ TCRhi cells within 3-4 d, indicative of positive selection. By adding the DNA precursor, bromodeoxyuridine, to the cultures and staining cells for bromodeoxyuridine incorporation, T cell division in reaggregation cultures was found to be high on day 1, low on day 2, and high on days 4-5. Cell separation studies established that cell division on day 1 was restricted to DP blast cells. In the absence of blast cells, small DP cells failed to proliferate and differentiated into SP cells without cell division, thus indicating that proliferation is not an essential component of positive selection. This applied to SP cells generated within the first 2-3 d. Surprisingly, the SP cells generated later in culture showed a high rate of cell division; the proliferating SP cells were TCRhi and included both CD4+8- and CD4-8+ cells. Turnover of TCRhi SP cells was also prominent in the normal neonatal thymus and in TEC reaggregation cultures prepared with adult lymph node T cells. We speculate that division of mature SP cells in the perinatal thymic microenvironment is driven by stimulatory cytokines released from TEC. Such proliferation could be a device to expand the mature T cell repertoire before export to the periphery.