Patel S S, Duby A D, Thiele D L, Lipsky P E
Harold C. Simmons Arthritis Research Center, Southwestern Medical School, Dallas 75235.
J Immunol. 1988 Dec 1;141(11):3726-36.
The capacity of human peripheral blood-derived T cell clones to carry out a variety of functions was examined. T cell clones were generated by stimulating individual peripheral blood T cells with PHA by a procedure that yielded a growing clone from a mean of greater than 92% of the cultured cells. A total of 65 T cell clones (44 CD4+ and 21 CD8+) generated from two individual donors were examined for their functional capabilities. All T cell clones examined secreted IL-2, IFN-gamma, and lymphotoxin/tumor necrosis factor like activity when stimulated with immobilized mAb to the CD3 complex (64.1). When 54 additional T cell clones from a third donor were analyzed, all were found to produce IL-2. Upon activation with immobilized 64.1, all CD4+ clones and 91% of the CD8+ clones induced the generation of Ig-secreting cells from purified B cells. The CD8+ clones that did not serve as Th cells alone were able to augment the capacity of fresh CD4+ cells to generate Ig-secreting cells. Each of these clones was also found to effect MHC-unrestricted cytotoxicity upon activation with immobilized 64.1. The CD8+ clones were somewhat more effective killers than CD4+ clones, although there was considerable overlap. A total of 18 clones was analyzed for TCR beta-chain gene rearrangement. Of the clones exhibiting rearrangements of the beta-chain gene, 94% were found to have a single rearrangement pattern. Finally, the detailed phenotype of 15 (11 CD4+ and 4 CD8+) of these clones was examined. Variable numbers of cells of each of the clones expressed Ag identified by mAb 4B4 (CD29), Leu 8, Leu 15 (CD11b), and NKH1. Moreover, cells of 6 of 11 CD4+ clones and 4 of 4 CD8+ clones also expressed CD45R in addition to CD29; expression of CD45R and CD29 varied with the activation status of the clone. The current data demonstrate that nearly all of the T cell clones were able to accomplish each of the functions examined regardless of the surface phenotype. Inasmuch as the clones were generated using a technique that expanded more than 92% of the circulating T cells, the data imply that the progeny of the vast majority of T cells may have the inherent capacity to exert a wide array of functional activities.
对源自人外周血的T细胞克隆执行多种功能的能力进行了检测。通过用PHA刺激单个外周血T细胞，采用一种从超过92%的培养细胞中产生生长克隆的方法来生成T细胞克隆。对来自两名个体供体的总共65个T细胞克隆（44个CD4 +和21个CD8 +）的功能能力进行了检测。当用针对CD3复合物的固定化单克隆抗体（64.1）刺激时，所有检测的T细胞克隆均分泌白细胞介素-2、γ-干扰素以及类淋巴毒素/肿瘤坏死因子活性。当对来自第三名供体的另外54个T细胞克隆进行分析时，发现所有克隆均产生白细胞介素-2。在用固定化的64.1激活后，所有CD4 +克隆以及91%的CD8 +克隆诱导纯化的B细胞产生分泌免疫球蛋白的细胞。单独不作为辅助性T细胞的CD8 +克隆能够增强新鲜CD4 +细胞产生分泌免疫球蛋白细胞的能力。还发现这些克隆中的每一个在用固定化的64.1激活后均具有MHC非限制性细胞毒性作用。CD8 +克隆作为杀伤细胞比CD4 +克隆稍有效，尽管存在相当大的重叠。对总共18个克隆进行了TCRβ链基因重排分析。在表现出β链基因重排的克隆中，94%被发现具有单一重排模式。最后，检测了其中15个克隆（11个CD4 +和4个CD8 +）的详细表型。每个克隆中不同数量的细胞表达由单克隆抗体4B4（CD29）、Leu 8、Leu 15（CD11b）和NKH1鉴定的抗原。此外，11个CD4 +克隆中的6个克隆以及4个CD8 +克隆中的4个克隆的细胞除了表达CD29外还表达CD45R；CD45R和CD29的表达随克隆的激活状态而变化。当前数据表明，几乎所有T细胞克隆无论表面表型如何都能够完成所检测的每种功能。由于这些克隆是使用一种使超过92%的循环T细胞扩增的技术产生的，数据表明绝大多数T细胞后代可能具有发挥广泛功能活性的内在能力。
