Differentiation and cell division in the mammalian thymus.
Differentiation and cell division in the mammalian thymus.
复制标题
哺乳动物胸腺的分化和细胞分裂。
DOI：
10.1016/0012-1606(85)90114-9
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发表时间：
1985
影响因子：
2.7
通讯作者：
Lugo,JP
中科院分区：
文献类型：
--
作者：
Rothenberg,E;Lugo,JP
胸腺产生的细胞在表型和行为上都有很大的不同。我们可以认为成熟的T细胞功能有三个组成部分。第一个是识别：识别和结合某些靶抗原结构的能力。第二种是通过分泌一系列本身不结合抗原的多肽介体对抗原作出反应的能力。功能的第三个组成部分是通过增殖对抗原作出反应的平行能力。T细胞对抗原的识别与大多数B细胞的识别不同，因为T细胞只能结合与另一细胞表面相关的抗原。这种“抗原识别”通过T细胞膜的大部分与另一个抗原呈递细胞的膜之间的相互作用而发生。为了发生结合，T细胞不仅必须接合标称外源抗原，而且还必须接合抗原呈递细胞上由主要组织相容性复合体（MHC）编码的特异性细胞表面糖蛋白。这种双重要求被称为MHC限制。其分子基础尚不清楚，尽管多个T细胞多肽参与结合抗原和MHC靶标（表1，II组）。标称T细胞受体（Ti）的α和β链参与通过其免疫球蛋白样可变区区分特定靶结构（Meuer等人，1984 a; Haskins等人，1984年）。它们由在表达之前经历组合重排的基因编码，使每个T细胞克隆具有独特的受体结构。某些类型的T细胞表达经历免疫球蛋白样重排的第三种密切相关基因的mRNA转录物，但尚未证明该“y”基因的蛋白质产物（Hayday et al.，1985年）。与01和fi物理相关并强制性共表达（Meuer et al.，1983; Reinherz等人，1983;韦斯和斯托博，1984）是一种三链多肽复合物T3，其深深嵌入膜中（Borst等人，1983 a，1983 b），并可能参与信号转导。在T细胞膜中独立于T1和T3扩散的分子对于稳定某些靶抗原复合物的结合也是重要的。Lyt 2（小鼠; Leu 2或T8）稳定与I类MHC结构的相互作用，和L3 T4（在小鼠中; Leu 3或T4在人中）稳定与II类结构的相互作用（Swain，1981; Wilde等，1983; Meuer等，1984年a）。Lyt 2或L3 T4的表达的丧失可以严重地降低T细胞的结合亲合力，足以改变其表观识别特异性，尽管其Ti-T3复合物是完整的（Dialynas等，1981; Marrack等，1983年）。如果T细胞以足够的亲合力结合抗原呈递细胞表面上的抗原，则可以触发T细胞。信号传导涉及内部Ca '+池的动员、蛋白激酶C激活和细胞内pH值的升高（图1; Tsien等人，1982; Berridge和Irvine，1984; Taylor等人，1984; Depper等人，1984; Hesketh等人，1985; Truneh等人，1985;因博登和斯托博，1985;格林斯坦等人，1985年）。这些变化的重要后果之一是T细胞特异性分泌反应。不同功能类别的T细胞具有不同的特征性分泌产物。辅助T细胞（Tu细胞）是免疫应答的正调节剂，刺激T和B细胞的生长和分泌，并增加B细胞的抗体产生。活化的Tn释放一系列生长和分化因子，如表1所列（III组）。在这些产品中有重要的T细胞生长激素，白细胞介素2（IL-2）。触发后介质的释放是缓慢的...
The cells produced by the thymus are highly distinctive in phenotype and in behavior. We can consider mature T-cell function to have three components. The first is recognition: the ability to discriminate and bind some target antigenic structure. The second is the ability to respond to the antigen by secreting a battery of polypeptide mediators which do not themselves bind the antigen. The third component of function is the parallel ability to respond to the antigen by proliferating. Recognition of antigens by T cells differs from recognition by most B cells in that T cells can only bind an antigen associated with the surface of another cell. Such “antigen recognition” occurs by means of the interaction between a large sector of the T-cell membrane and the membrane of the other, antigen-presenting cell. For binding to occur, the T cell must engage not only the nominal foreign antigen but also specific cell surface glycoproteins, encoded by the major histocompatibility complex (MHC), on the antigen-presenting cell. This dual requirement is called MHC restriction. Its molecular basis is not known in detail, although multiple T-cell polypeptides are implicated in binding antigen and MHC targets (Table 1, group II). The a and p chains of the nominal T-cell receptor (Ti) are involved in discriminating specific target structures through their immunoglobulin-like variable regions (Meuer et ah, 1984a; Haskins et al., 1984). They are encoded by genes which undergo combinatorial rearrangements prior to being expressed, giving each T-cell clone a distinctive receptor structure. Certain classes of T cells express mRNA transcripts of a third, closely related gene that undergoes immunoglobulin-like rearrangements, but the protein product of this “y” gene has not yet been demonstrated (Hayday et al., 1985). Physically associated and obligatorily coexpressed with 01 and fi (Meuer et al., 1983; Reinherz et al., 1983; Weiss and Stobo, 1984) is a three-chain polypeptide complex, T3, which is deeply embedded in the membrane (Borst et al., 1983a, 1983b) and possibly involved in signal transduction. Molecules that diffuse independently of Ti and T3 in the T-cell membrane are also important for stabilizing the binding of certain target antigen complexes. Lyt2 (in mice; Leu2 or T8 in humans) stabilizes interactions with class I MHC structures, and L3T4 (in mice; Leu3 or T4 in humans) those with class II structures (Swain, 1981; Wilde et al, 1983; Meuer et al., 1984a). The loss of expression of Lyt2 or L3T4 can lower the binding avidity of a T cell severely enough to change its apparent recognition specificity, although its Ti-T3 complexes are intact (Dialynas et ah, 1981; Marrack et al., 1983). If the T cell binds antigen on the surface of the antigen-presenting cell with sufficient avidity, then the T cell can be triggered. Signal transduction involves the mobilization of internal Ca’+ pools, protein kinase C activation, and an increase in intracellular pH (Fig. 1; Tsien et al., 1982; Berridge and Irvine, 1984; Taylor et al., 1984; Depper et al., 1984; Hesketh et al., 1985; Truneh et al., 1985; Imboden and Stobo, 1985; Grinstein et al., 1985). Among the important consequences of these changes are T-cell-specific secretory responses. Different functional classes of T cells have different characteristic secretory products. Helper T cells (Tu cells) are the positive regulators of the immune response, stimulating growth and secretion by T and B cells and augmenting antibody production by B cells. Activated Tn release an array of growth and differentiation factors, as listed in Table 1 (group III). Among these products is the vital T-cell growth hormone, interleukin 2 (IL-2).’The release of the mediators after triggering is slow …