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仓鼠T细胞亚群的发育与个体发生

Development and ontogeny of hamster T cell subpopulations.

作者信息

Witte P L, Streilein J W

出版信息

J Immunol. 1986 Jul 1;137(1):45-54.

PMID:3486916
Abstract

The Syrian hamster is unique among laboratory animals because products of class I MHC genes are monomorphic. Thus, this species may be a model in which to test the relationship between MHC polymorphism and the T cell antigen receptor repertoire. Recently, cytotoxic and helper T cell subpopulations have been distinguished on the basis of cell surface phenotype detected with monoclonal antibodies (mAb). We used these reagents (mAb 110 detects all peripheral T cells and mAb 38 detects cytotoxic T cells) to dissect and categorize thymic populations according to relative maturational status. The two mAb divide thymocytes into four subpopulations in the young adult. Two (110+ 38+, 110+ 38-) were peripheral-like and were housed in the medulla, exclusively; another subset (110- 38+) consisted almost entirely of TdT+ cortical thymocytes. The fourth subset (110- 38-), bearing neither marker, was heterogeneous and consisted mostly of medium-large-size thymocytes, including cells with an early phenotype (nuclear TdT+). Cells with the cortical phenotype proved to be the most sensitive to cortisone treatment, whereas those which expressed the medullary marker, 110, were most resistant. To ascertain the relationship between 110- and 110+ T lineage cells, we followed the appearance of the four thymic subpopulations during ontogeny of the hamster thymus. Adult-like thymic architecture (delineation of cortex and medulla) as well as the two 110- subsets were established before expression of 110 antigen was apparent in the thymus. However, lymphocytes bearing the 110 antigen were found in lymph nodes prior to thymus during ontogeny, concomitant with developing T cell function in peripheral tissue. This finding implies that cells lacking 110 antigen were exported from the thymus and subsequently acquired expression of the molecule in the periphery, and we suggest that acquisition of 110 antigen may be a stage of postthymic maturation. Although 110+ cells appeared to be the most mature subset by several criteria, all functional thymocytes of adults or neonates were not 110+. Thus, we conclude that the 110 marker is acquired after T cells reach functional maturity. Moreover, the response profile of isolated 38+ thymocytes was analogous to peripheral 38+ T cells, suggesting that the dichotomy of function detected with our mAb also occurs before acquisition of 110 antigen. We have modeled what is known about hamster T cell development into a hypothetical scheme.

摘要

叙利亚仓鼠在实验动物中很独特,因为其I类主要组织相容性复合体(MHC)基因产物是单态的。因此,该物种可能是一个用于测试MHC多态性与T细胞抗原受体库之间关系的模型。最近,已根据用单克隆抗体(mAb)检测到的细胞表面表型区分出细胞毒性T细胞亚群和辅助性T细胞亚群。我们使用这些试剂(mAb 110可检测所有外周T细胞,mAb 38可检测细胞毒性T细胞)根据相对成熟状态对胸腺群体进行剖析和分类。这两种mAb将成年早期的胸腺细胞分为四个亚群。其中两个亚群(110 + 38 +、110 + 38 -)类似外周细胞,仅存在于髓质中;另一个亚群(110 - 38 +)几乎完全由末端脱氧核苷酸转移酶(TdT)阳性的皮质胸腺细胞组成。第四个亚群(110 - 38 -)既不带有这两种标记,细胞异质性高,主要由中等大小和大尺寸的胸腺细胞组成,包括具有早期表型(核TdT阳性)的细胞。具有皮质表型的细胞被证明对可的松处理最敏感,而那些表达髓质标记110的细胞最具抗性。为了确定110阴性和110阳性T细胞系细胞之间的关系,我们追踪了仓鼠胸腺个体发育过程中四个胸腺亚群的出现情况。在胸腺中110抗原表达明显之前,就已建立了类似成年的胸腺结构(皮质和髓质的划分)以及两个110阴性亚群。然而,在个体发育过程中,在胸腺之前的淋巴结中就发现了带有110抗原的淋巴细胞,这与外周组织中T细胞功能的发育同时发生。这一发现意味着缺乏110抗原的细胞从胸腺输出,随后在周围组织中获得该分子的表达,并且我们认为获得110抗原可能是胸腺后成熟的一个阶段。尽管从几个标准来看110阳性细胞似乎是最成熟的亚群,但成年或新生动物的所有功能性胸腺细胞并非都是110阳性。因此,我们得出结论,110标记是在T细胞达到功能成熟后获得的。此外,分离出的38阳性胸腺细胞的反应谱与外周38阳性T细胞类似,这表明用我们的mAb检测到的功能二分法也发生在获得110抗原之前。我们已将关于仓鼠T细胞发育的已知信息构建成一个假设方案。

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