Marshall J D, Wen Y, Abrams J S, Umetsu D T
Department of Pediatrics, Stanford University, California 94305-5119.
Cell Immunol. 1993 Nov;152(1):18-34. doi: 10.1006/cimm.1993.1264.
Although Th2 helper cell clones produce IL-4 and IL-5, CD4+ T cells taken fresh from lymphoid organs of mice produce IL-2 and some IFN-gamma, but not IL-4 or IL-5. The exact parameters that enhance the synthesis of IL-4, IL-5, and particularly IL-10 from resting antigen-specific CD4+ T cells is not yet clear. We therefore examined the kinetics of, and the parameters that affect, the development of IL-4, IL-5, and IL-10 production in bulk populations of antigen-specific human CD4+ T cells. We demonstrated that in vitro stimulation of human peripheral blood lymphocytes with antigen (tetanus toxoid or a viral antigen, Varicella zoster) for several days resulted in the production of IL-2 and IFN-gamma, but little or no IL-4 or IL-5. This cytokine profile was observed even when CD4+ T cells from allergic donors were stimulated once in vitro with allergen (rye grass pollen, Lolium perenne I, or dust mite allergen, Dermatophagoides farinae). The observed cytokine profile reflected that of the vast majority of antigen-specific T cells, since we studied the response of bulk populations of CD4+ T cells rather than that of a "selected" number of antigen-specific T cell clones. Furthermore, we observed that human CD4+ T cells from either allergic or nonallergic individuals failed to produce significant quantities of IL-4, IL-5, or IL-10 even after several rounds of stimulation with soluble protein (nonallergen) antigens such as tetanus toxoid or Var. z. However, large quantities of these cytokines were produced when stimulation of the T cells occurred in the presence of rIL-4, but only after two stimulations in vitro with antigen over a period of greater than 7 days. In addition, substantial quantities of IL-4, IL-5, and IL-10 were produced by CD4+ T cells from allergic subjects in the absence of exogenous IL-4, but only after two stimulations in vitro with allergens such as rye grass pollen or dust mite allergen. These results indicate that the development of IL-4 and IL-5 synthesis occurs in peripheral blood CD4+ T cells in a stepwise fashion, first with the production of IL-2 and IFN-gamma, and later with the production of IL-4 and IL-5.(ABSTRACT TRUNCATED AT 250 WORDS)
虽然Th2辅助性T细胞克隆可产生白细胞介素-4（IL-4）和白细胞介素-5（IL-5），但从小鼠淋巴器官中新鲜获取的CD4+ T细胞可产生IL-2和一些干扰素-γ（IFN-γ），但不产生IL-4或IL-5。增强静息抗原特异性CD4+ T细胞合成IL-4、IL-5，尤其是IL-10的确切参数尚不清楚。因此，我们研究了抗原特异性人CD4+ T细胞群体中IL-4、IL-5和IL-10产生的动力学以及影响其产生的参数。我们发现，用人外周血淋巴细胞在体外与抗原（破伤风类毒素或病毒抗原水痘带状疱疹病毒）刺激数天可导致IL-2和IFN-γ的产生，但IL-4或IL-5产生很少或不产生。即使在体外将来自过敏供体的CD4+ T细胞用过敏原（黑麦草花粉、多年生黑麦草I或尘螨过敏原粉尘螨）刺激一次，也观察到这种细胞因子谱。观察到的细胞因子谱反映了绝大多数抗原特异性T细胞的情况，因为我们研究的是CD4+ T细胞群体的反应，而不是“选定”数量的抗原特异性T细胞克隆的反应。此外，我们观察到，即使在用破伤风类毒素或水痘带状疱疹病毒等可溶性蛋白（非过敏原）抗原进行几轮刺激后，来自过敏或非过敏个体的人CD4+ T细胞仍无法产生大量的IL-4、IL-5或IL-10。然而，当在重组人IL-4（rIL-4）存在的情况下刺激T细胞时，会产生大量这些细胞因子，但前提是在体外经过超过7天的时间用抗原进行两次刺激。此外，在没有外源性IL-4的情况下，过敏受试者的CD4+ T细胞在体外仅用黑麦草花粉或尘螨过敏原等过敏原进行两次刺激后，就会产生大量的IL-4、IL-5和IL-10。这些结果表明，外周血CD4+ T细胞中IL-4和IL-5合成的发展是逐步进行的，首先产生IL-2和IFN-γ，随后产生IL-4和IL-5。（摘要截短至250字）
