Moretta L, Ciccone E, Mingari M C, Bottino C, Ferrini S, Tambussi G, Melioli G, Grossi C E, Moretta A
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Clin Immunol Immunopathol. 1989 Jan;50(1 Pt 2):S117-23. doi: 10.1016/0090-1229(89)90118-9.
The majority of mature T lymphocytes express CD3-associated antigen receptor molecules (TCR) formed by alpha and beta chains. Recently, a minor subset has been identified that expresses a different CD3-associated heterodimer composed of gamma and delta chains. The TCR gamma/delta+ cell subset differs from conventional T cells for a number of phenotypic and functional characteristics. The simultaneous lack of both CD4 and CD8 antigens allows to greatly enrich TCR gamma/delta+ cells (by monoclonal antibodies and complement). Cloning of CD4-8- peripheral blood lymphocytes, under limiting dilution conditions, revealed that they are homogeneously composed of cytolytic cells which, in most instances, lyse tumor target cells. The formal proof has been provided that TCR gamma/delta+ cells are able to recognize antigens. Indeed they proliferated in response to allogeneic cells in mixed lymphocyte culture (MLC) and MLC-derived TCR gamma/delta+ cells specifically lysed PHA-induced blast cells bearing the stimulating alloantigens. The use of different monoclonal antibodies specific for TCR gamma/delta molecules allowed to identify two distinct subsets which bound BB3 and delta-TCS-1 mAbs, respectively. The BB3-reactive TCR molecules were represented by C gamma 1-encoded disulfide-linked heterodimers, whereas delta-TCS-1 reacted with C gamma 2-encoded nondisulfide-linked molecules. Both BB3 and delta-TCS-1 mAb induced activation of cloned cells expressing the corresponding antigenic determinants (as assessed by measurements of intracellular Ca2+ and lymphokine production or cytolytic activity). Analysis of the unfrequent delta-TCS-1+ clones which express surface CD8 molecules revealed that the "heavy" 55 kDa form of (C gamma 2-encoded) gamma chain is selectively expressed by this cell type. Analysis of the distribution of subsets expressing different TCR gamma/delta isotypes showed that the C gamma 1-encoded, BB3-reactive form is prevalent in the peripheral blood, but virtually absent in the thymus. In contrast, cells expressing the C gamma 2-encoded, delta-TCS-1 reactive form are relatively unfrequent in peripheral blood, but represent the majority of TCR gamma/delta+ thymocytes. In addition, upon culture in rIL-2, approximately half of the delta-TCS-1+ thymocytes expressed CD8 antigen, thus providing further evidence that major differences exist in the distribution of TCR gamma/delta+ subsets in thymus and in peripheral blood.
大多数成熟的T淋巴细胞表达由α链和β链组成的与CD3相关的抗原受体分子（TCR）。最近，已鉴定出一个较小的亚群，其表达由γ链和δ链组成的不同的与CD3相关的异二聚体。TCRγ/δ+细胞亚群在许多表型和功能特征上与传统T细胞不同。同时缺乏CD4和CD8抗原使得能够通过单克隆抗体和补体极大地富集TCRγ/δ+细胞。在有限稀释条件下对CD4- CD8-外周血淋巴细胞进行克隆，结果显示它们均一性地由溶细胞性细胞组成，在大多数情况下，这些细胞可裂解肿瘤靶细胞。已经提供了正式证据表明TCRγ/δ+细胞能够识别抗原。实际上，它们在混合淋巴细胞培养（MLC）中对同种异体细胞产生增殖反应，并且MLC来源的TCRγ/δ+细胞特异性地裂解带有刺激同种异体抗原的PHA诱导的母细胞。使用针对TCRγ/δ分子的不同单克隆抗体能够鉴定出两个不同的亚群，它们分别与BB3和δ-TCS-1单克隆抗体结合。与BB3反应的TCR分子由Cγ1编码的二硫键连接的异二聚体代表，而δ-TCS-1与Cγ2编码的非二硫键连接的分子反应。BB3和δ-TCS-1单克隆抗体均诱导表达相应抗原决定簇的克隆细胞活化（通过测量细胞内Ca2+以及淋巴因子产生或溶细胞活性来评估）。对表达表面CD8分子的罕见的δ-TCS-1+克隆进行分析发现，这种细胞类型选择性地表达（Cγ2编码的）γ链的“重”55 kDa形式。对表达不同TCRγ/δ同种型的亚群分布进行分析表明，Cγ1编码的、与BB3反应的形式在外周血中占优势，但在胸腺中几乎不存在。相反，表达Cγ2编码的、与δ-TCS-1反应的形式的细胞在外周血中相对较少，但占TCRγ/δ+胸腺细胞的大多数。此外，在rIL-2中培养后，大约一半的δ-TCS-1+胸腺细胞表达CD8抗原，从而进一步证明胸腺和外周血中TCRγ/δ+亚群的分布存在主要差异。
