Pharmacological modification of immunoregulatory activity of lymphocytes: facts and potential.

Pharmacological modification of immunoregulatory activity of lymphocytes: facts and potential.
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淋巴细胞免疫调节活性的药理学修饰:事实和潜力。

DOI:
10.1007/bf02919043
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发表时间:
1984
期刊:
Survey of immunologic research
影响因子:
--
通讯作者:
Polmar,SH
Polmar,SH
中科院分区:
--
文献类型:
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作者:
Polmar,SH

文献摘要

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在过去的5年中,我们对免疫调节机制的了解迅速扩大,这在很大程度上是由于通过应用单抗技术来描绘淋巴细胞亚群。在人类中,OKT和Leu系列单抗被最广泛地用于T淋巴细胞分化的研究和免疫调节淋巴细胞亚群的鉴定[1]。在T淋巴细胞胸腺内分化过程中,胸腺细胞和成熟T细胞上的抗原依次出现和消失,从而产生了OKT和Leu单抗检测到的抗原代表“分化抗原”的概念[2]。虽然大多数胸腺细胞在其表面表达T10、T6、T4和T8抗原,但在胸腺分化后期,TI0和T6抗原丢失,而T3‘PAN T细胞’抗原表达。此外,T4和T8抗原在胸腺内成熟后期分离,因此在外周血和外周淋巴组织中只发现具有T3+T4+或L的成熟T细胞,这些T细胞得到美国公共卫生服务、美国国立卫生研究院的研究资助(AI 17570、AI 20086和CA 38353)支持。最初发现T3+T4+细胞亚群含有促进B细胞分化和免疫球蛋白合成的细胞(T辅助/诱导细胞),以及激活细胞毒性T淋巴细胞和T抑制细胞所需的细胞。促进B细胞分化的T3+T4+细胞现在可以与那些使用特定抗体诱导抑制细胞激活的细胞区分开来[3]。最近的研究还表明,具有T4+表面表型的一部分细胞可能会“反馈”T辅助细胞以抑制其功能[4]。T抑制淋巴细胞和T细胞毒性淋巴细胞均具有T_3+T_8~+表型。最近开发的单抗也可以描述不同的抑制子和细胞毒性亚群。因此,利用T淋巴细胞表面抗原的单抗可以鉴定人类淋巴细胞亚群中相当大的异质性。虽然这种异质性很大程度上是在胸腺内分化过程中产生的,但越来越多的证据表明胸腺后细胞表面抗原表达的变化。
The rapid expansion in our understanding of immunoregulatory mechanisms which has occurred during the last 5 years has largely been due to the delineation of lymphocyte subpopulations through the application of monoclonal antibody techniques. In man the OKT and Leu series of monoclonal antibodies have been most extensively used for the study of T-lymphocyte differentiation and identification of immunoregulatory lymphocyte subpopulations [1]. During intrathymic differentiation of T lymphocytes there is sequential appearance and disappearance of antigens upon thymocytes and maturing T cells giving rise to the notion that the antigens detected by the OKT and Leu monoclonal antibodies represent'differentiation antigens'[2]. While most thymocytes express the T10, T6, T4 and T8 antigens on their surfaces, the TI0 and T6 antigens are lost during late intrathymic differentiation and the T3'pan T-cell'antigen is expressed. Moreover, the T4 and T8 antigens segregate during late intrathymic maturation such that only mature T cells with the T3+ T4+ or l Supported by research grants (AI 17570, AI 20086 and CA 38353) from the US Public Health Service, National Institutes of Health~ DHHS.T3+ T8+ surface phenotypes are found in peripheral blood and peripheral lymphoid tissues. The T3+ T4+ cell subpopulation was initially found to contain those cells (T-helper/inducer cells) which facilitated B-cell differentiation and immunoglobulin synthesis as well as those cells required for activation of cytotoxic T-lymphocytes and T-suppressor cells. The T3+ T4+ cells which facilitate B-cell differentiation can now be distinguished from those which induce suppressor cell activation with the use of specific antibodies [3]. Recent studies have also indicated that a subset of cells with the T4+ surface phenotype may'feed back'upon T-helper cells to inhibit their functions [4]. Both T-suppressor and T-cytotoxic lymphocytes have the T3+ T8+ surface phenotype. Recently developed monoclonal antibodies also permit the delineation of distinct suppressor and cytotoxic subpopulations. Thus, considerable heterogeneity within human lymphocyte subpopulations may be identified by the use of monoclonal antibodies to T-lymphocyte surface antigens. While much of this heterogeneity is clearly generated in the course of intrathymic differentiation, there is growing evidence for postthymic alteration of cell surface antigen expression.