Rotteveel F T, Kokkelink I, van Lier R A, Kuenen B, Meager A, Miedema F, Lucas C J
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
J Exp Med. 1988 Nov 1;168(5):1659-73. doi: 10.1084/jem.168.5.1659.
A large number of CD4+ T cell clones, obtained from peripheral blood T lymphocytes by direct limiting dilution, allowed us to address the question whether functional heterogeneity exists within the human CD4+ T cell subset. Cytotoxic capacity of cloned T cells was analyzed with the use of anti-CD3 antibodies and target cells bearing FcR for murine IgG. 6 of 12 CD4+ clones obtained were able to lyse Daudi or P815 cells in the presence of anti-CD3 antibodies. The remaining six CD4+ T cell clones tested did not display anti-CD3-mediated cytotoxic activity and did not acquire this cytotoxic capacity during a culture period of 20 wk. In the absence of anti-CD3 mAb, no lytic activity against Daudi, P815, and K562 target cells was observed under normal culture conditions. Phenotypic analysis of these two distinct types of CD4+ T cells did not reveal differences with regard to reactivity with CDw29 (4B4) and CD45R (2H4) mAbs that have been described to recognize antigens associated with helper suppressor/inducer (respectively) CD4+ cells. The CD4+ clones without anti-CD3-mediated cytotoxic activities (Th2) consistently showed a high expression level of CD28 antigens, whereas the cytotoxic clones (Th1) expressed low amounts of CD28. Th1 CD4+ clones did produce IL-2, IFN-gamma, and TNF-alpha/beta, whereas the Th2 T cell clones produced minimal amounts of IL-2 and only low levels of INF-gamma and TNF-alpha/beta in response to anti-CD3 mAbs and PMA. Although not all CD4+ clones did release IL-4, there was no correlation with cytotoxic activity. Moreover, as compared with the Th1 CD4+ clones, Th2 CD4+ T cell clones proliferated moderately in response to immobilized anti-CD3 mAbs. However, proliferation reached the level of the cytotoxic clones when anti-CD28 mABs were present during culture. Both CD4+ subsets provided help for B cell differentiation upon stimulation with anti-CD3 mAbs. Our data suggest that the human CD4+ subset, in analogy to the murine system, comprises two functionally distinct T cell subpopulations, both of which are able to exert helper activity for polyclonal B cell differentiation, but which differ in cytotoxic capacity, lymphokine production, and requirements for proliferation. A function for these two types of T cells in the immune response is discussed.
通过直接有限稀释从外周血T淋巴细胞中获得的大量CD4 + T细胞克隆，使我们能够探讨人类CD4 + T细胞亚群中是否存在功能异质性的问题。利用抗CD3抗体和带有鼠IgG FcR的靶细胞分析克隆T细胞的细胞毒性能力。在获得的12个CD4 +克隆中，有6个在抗CD3抗体存在的情况下能够裂解Daudi或P815细胞。其余6个测试的CD4 + T细胞克隆未显示抗CD3介导的细胞毒性活性，并且在20周的培养期内未获得这种细胞毒性能力。在没有抗CD3 mAb的情况下，在正常培养条件下未观察到对Daudi、P815和K562靶细胞的裂解活性。对这两种不同类型的CD4 + T细胞进行表型分析，未发现它们在与已描述分别识别与辅助抑制/诱导（分别）CD4 +细胞相关抗原的CDw29（4B4）和CD45R（2H4）mAb的反应性方面存在差异。没有抗CD3介导的细胞毒性活性的CD4 +克隆（Th2）始终显示出CD28抗原的高表达水平，而具有细胞毒性的克隆（Th1）表达的CD28量较低。Th1 CD4 +克隆确实产生IL-2、IFN-γ和TNF-α/β，而Th2 T细胞克隆在响应抗CD3 mAb和PMA时产生的IL-2量极少，IFN-γ和TNF-α/β水平也很低。虽然并非所有CD4 +克隆都释放IL-4，但这与细胞毒性活性无关。此外，与Th1 CD4 +克隆相比，Th2 CD4 + T细胞克隆在响应固定化抗CD3 mAb时增殖适度。然而，当培养期间存在抗CD28 mAB时，增殖达到了具有细胞毒性克隆的水平。在用抗CD3 mAb刺激时，两个CD4 +亚群都为B细胞分化提供帮助。我们的数据表明，与小鼠系统类似，人类CD4 +亚群包含两个功能不同的T细胞亚群，两者都能够对多克隆B细胞分化发挥辅助活性，但在细胞毒性能力、淋巴因子产生和增殖需求方面存在差异。讨论了这两种类型的T细胞在免疫反应中的功能。
