Hirohata S, Patel S S, Lipsky P E
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235.
Cell Immunol. 1990 Apr 15;127(1):35-46. doi: 10.1016/0008-8749(90)90112-5.
Previous studies have shown that human CD8-positive T cells activated by immobilized mAb to the CD3 complex have the capacity to support the generation of Ig secreting cells (ISC). The experiments reported here were undertaken to examine the nature of CD8+ T cell helper function in greater detail. CD8+ T cells that had been treated with mitomycin C (CD8+ mito) and stimulated by immobilized mAb to CD3 (64.1) provided help for the generation of ISC from resting B cells. By contrast, CD8+ mito did not support the generation of ISC in cultures stimulated by pokeweed mitogen (PWM). This could not be explained by differences in the production of IL2, since PWM and anti-CD3 induced comparable amounts of IL2 from CD8+ mito. In anti-CD3-stimulated cultures, CD8+ mito supported the generation of larger numbers of ISC when B cells were also activated with Staphylococcus aureus (SA). By contrast, in PWM-stimulated cultures, CD8+ mito did not provide help for SA-activated B cells. Rather, PWM-stimulated CD8+ mito appeared to suppress the generation of ISC induced by PWM-activated CD4+ mito or by SA + IL2, whereas anti-CD3-stimulated CD8+ mito did not. Only control CD8+ T cells, which were able to proliferate, exerted suppressive effects in anti-CD3-stimulated cultures. Examination of the functional capacities of a battery of CD8+ T cell clones indicated that the same clonal population of CD8+ cells could provide help or suppress responses when stimulated with anti-CD3 or PWM, respectively. The functional activities of CD8+ clones differed from those of fresh CD8+ cells. Thus, anti-CD3-stimulated CD8+ clones provided help for B cells regardless of whether they were treated with mitomycin C. Moreover, PWM stimulated suppression by CD8+ clones was abrogated by treating the clones with radiation or mitomycin C. These results indicate that helper T cell function is not limited to the CD4+ T cell population, but that help can also be provided by appropriately stimulated CD8+ T cells. Taken together, these results indicate that CD8+ T cells are not limited in their capacity to regulate B cell responses, but rather can provide positive or negative influences depending on the nature of the activating stimulus.
先前的研究表明，被固定化抗CD3复合物单克隆抗体激活的人CD8阳性T细胞有能力支持分泌免疫球蛋白细胞（ISC）的产生。此处报告的实验旨在更详细地研究CD8+ T细胞辅助功能的本质。用丝裂霉素C处理过的CD8+ T细胞（CD8+ mito），并被固定化抗CD3单克隆抗体（64.1）刺激后，能为静息B细胞产生ISC提供帮助。相比之下，CD8+ mito在商陆有丝分裂原（PWM）刺激的培养物中不支持ISC的产生。这不能用IL2产生的差异来解释，因为PWM和抗CD3从CD8+ mito诱导出的IL2量相当。在抗CD3刺激的培养物中，当B细胞也用金黄色葡萄球菌（SA）激活时，CD8+ mito支持产生更多数量的ISC。相比之下，在PWM刺激的培养物中，CD8+ mito不为SA激活的B细胞提供帮助。相反，PWM刺激的CD8+ mito似乎抑制由PWM激活的CD4+ mito或SA + IL2诱导的ISC的产生，而抗CD3刺激的CD8+ mito则不会。只有能够增殖的对照CD8+ T细胞在抗CD3刺激的培养物中发挥抑制作用。对一系列CD8+ T细胞克隆的功能能力进行检测表明，同一克隆群体的CD8+细胞在用抗CD3或PWM刺激时，分别可以提供帮助或抑制反应。CD8+克隆的功能活性与新鲜CD8+细胞不同。因此，抗CD3刺激的CD8+克隆无论是否用丝裂霉素C处理，都能为B细胞提供帮助。此外，用辐射或丝裂霉素C处理克隆可消除PWM刺激的CD8+克隆的抑制作用。这些结果表明，辅助性T细胞功能并不局限于CD4+ T细胞群体，适当刺激的CD8+ T细胞也能提供帮助。综上所述，这些结果表明，CD8+ T细胞调节B细胞反应的能力并不局限于此，而是可以根据激活刺激的性质提供正向或负向影响。
