CD4+ T淋巴细胞的功能异质性：用单克隆抗体WR16和WR19鉴定出具有相互拮抗免疫调节功能的两个亚群。

Functional heterogeneity of CD4+ T lymphocytes: two subpopulations with counteracting immunoregulatory functions identified with the monoclonal antibodies WR16 and WR19.

作者信息

Moore K, Nesbitt A M

出版信息

Immunology. 1987 Jun;61(2):159-65.

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1453371/

Abstract

Monoclonal antibodies (MoAbs) WR16 and WR19 bound to 47% and 43% of CD4+ tonsil T lymphocytes, respectively. WR16 immunoprecipitated a 220,000 molecular weight (MW) component that was also expressed on CD8+ lymphocytes and on B lymphocytes, whereas binding of WR19 was restricted to CD4+ lymphocytes. Binding of these two MoAbs on freshly prepared tonsil CD4+ T lymphocytes was mutually exclusive, and they were used to prepare reciprocal CD4+ subpopulations by negative depletion using the panning technique. Recombination of subsets isolated in this way with autologous B lymphocytes activated with pokeweed mitogen demonstrated that WR16+/OKT4+ lymphocytes suppressed B lymphocyte Ig secretion, whereas WR19+/OKT4+ lymphocytes helped B lymphocyte Ig secretion. Removal of WR16+ cells from a CD4+ helper cell population enhanced B lymphocyte Ig secretion rate, whilst the re-addition of WR16+ cells to WR19+ helper cells reduced B lymphocyte Ig secretion rates to that seen with non-fractionated CD4+ helper cells. The overall level of helper activity induced by a given CD4+ population was thus a consequence of an interaction between WR19+ helper cells and WR16+ suppressor cells. The WR16+ subset of CD4+ cells exhibited a greater proliferation rate than WR19+/CD4+ cells in response to mitogen. Proliferation of negatively selected WR16+/CD4+ lymphocytes was inhibited by pretreatment with WR16, which also induced a concomitant increase in the level of suppressor activity of these cells. Expression of the antigens identified by these two MoAbs was not constant as phytohaemagglutinin activation of T lymphocytes induced a loss of WR16 binding with a simultaneous increase in the level of WR19 bound/cell and in the proportion of WR19+ cells. T lymphocyte clones selected from a normal population were composed of a disproportionately high number positive for WR19 and negative for WR16. These data indicated that the absence of the WR19 antigen on WR16+ cells may be transient as the antigen was acquired by the majority of CD4+ T lymphocytes after activation. These two MoAbs may therefore be used to predict the functional status of a heterogeneous population of CD4+ lymphocytes and may also prove to be of use in the study of CD4+ T lymphocyte activation.

摘要

单克隆抗体（MoAbs）WR16和WR19分别与47%和43%的CD4⁺扁桃体T淋巴细胞结合。WR16免疫沉淀出一种分子量为220,000（MW）的成分，该成分也在CD8⁺淋巴细胞和B淋巴细胞上表达，而WR19的结合则仅限于CD4⁺淋巴细胞。这两种单克隆抗体在新鲜制备的扁桃体CD4⁺T淋巴细胞上的结合是相互排斥的，并且它们被用于通过淘选技术进行阴性去除来制备相互对应的CD4⁺亚群。将以这种方式分离的亚群与用美洲商陆丝裂原激活的自体B淋巴细胞重组，结果表明WR16⁺/OKT4⁺淋巴细胞抑制B淋巴细胞Ig分泌，而WR19⁺/OKT4⁺淋巴细胞促进B淋巴细胞Ig分泌。从CD4⁺辅助细胞群体中去除WR16⁺细胞可提高B淋巴细胞Ig分泌率，而将WR16⁺细胞重新添加到WR19⁺辅助细胞中则会使B淋巴细胞Ig分泌率降低至未分离的CD4⁺辅助细胞时的水平。因此，给定CD4⁺群体诱导的辅助活性的总体水平是WR19⁺辅助细胞和WR16⁺抑制细胞之间相互作用的结果。CD4⁺细胞的WR16⁺亚群在对丝裂原的反应中表现出比WR19⁺/CD4⁺细胞更高的增殖率。用WR16预处理可抑制阴性选择的WR16⁺/CD4⁺淋巴细胞的增殖，这也会导致这些细胞的抑制活性水平同时增加。这两种单克隆抗体识别的抗原表达并不恒定，因为T淋巴细胞的植物血凝素激活会导致WR16结合丧失，同时结合的WR19水平以及WR19⁺细胞的比例会增加。从正常群体中选择的T淋巴细胞克隆中，WR19阳性且WR16阴性的细胞数量不成比例地高。这些数据表明，WR16⁺细胞上WR19抗原的缺失可能是短暂性的，因为大多数CD4⁺T淋巴细胞在激活后会获得该抗原。因此，这两种单克隆抗体可用于预测异质性CD4⁺淋巴细胞群体的功能状态，也可能在CD4⁺T淋巴细胞激活的研究中有用。