Croft M, Carter L, Swain S L, Dutton R W
Department of Biology and Cancer Center, University of California San Diego, La Jolla 92093-0063.
J Exp Med. 1994 Nov 1;180(5):1715-28. doi: 10.1084/jem.180.5.1715.
We have generated primary effector populations from naive CD8 T cells in response to antigen and determined their patterns of cytokine secretion upon restimulation. The effect of exogenous factors on the effector generation was examined and compared with responses of antigen-specific CD4 effectors generated under comparable conditions. CD8 cells from bm1 mice were stimulated with C57BL/6 (B6) antigen presenting cells (APCs) bearing allogeneic class I and CD8 cells from female severe combined immunodeficiency (SCID) B6 mice, transgenic for a T cell receptor alpha/beta (TCR-alpha/beta) that recognizes H-Y on Db, were stimulated with APCs from male mice. In parallel, CD4 cells from bm12 mice were stimulated with alloantigen and CD4 cells from V beta 3/V alpha 11 TCR transgenics were stimulated with a peptide of pigeon cytochrome c on IEk. T cells from both transgenic mice were of naive phenotype whereas normal mice contained 10-20% memory cells. Effector CD8 populations generated were L-selectin low, CD45RB high, and CD44 high. Naive CD8 cells from SCID anti-H-Y mice made little or no cytokine immediately upon stimulation in contrast to naive CD4 which produced large amounts of interleukin 2 (IL-2). Both populations, however, generated primary effectors over 4-5 d that made substantial quantities of many cytokines upon restimulation. Both CD8 and CD4 effectors produced similar patterns of cytokines with alloantigen or specific antigen. Cytokines present during naive CD8 stimulation influenced the cytokine secretion profile of the effectors, as previously shown for CD4 cells, although secretion by CD8 effectors was generally lower than that of CD4 effectors. CD8 cells cultured with IL-2 alone made predominantly interferon gamma (IFN-gamma) and no IL-4 or IL-5, similar to CD4 cells. Priming with IFN-gamma increased IFN-gamma secretion from CD4 effectors, but had little if any effect on CD8 cells. In contrast, priming with IL-12 generated CD8 effectors, as well as CD4 effectors, producing elevated quantities of IFN-gamma, with similar levels from both the CD4 and CD8 populations. The presence of IL-4 during effector cell generation promoted synthesis of IL-4 and IL-5 from both CD8 and CD4 cells while downregulating IFN-gamma secretion. CD8 cells made only small amounts of IL-4, more than 100-fold less than CD4 cells, whereas significant levels of IL-5 were induced, only 3-10-fold lower than from CD4.(ABSTRACT TRUNCATED AT 400 WORDS)
我们从初始CD8 T细胞中诱导出了主要效应细胞群体，使其对抗原作出反应，并在再次刺激后确定了它们的细胞因子分泌模式。研究了外源性因子对效应细胞生成的影响，并与在类似条件下产生的抗原特异性CD4效应细胞的反应进行了比较。用携带同种异体I类分子的C57BL/6（B6）抗原呈递细胞（APC）刺激bm1小鼠的CD8细胞，用识别Db上H-Y的T细胞受体α/β（TCR-α/β）转基因的雌性重症联合免疫缺陷（SCID）B6小鼠的CD8细胞，用雄性小鼠的APC进行刺激。同时，用同种异体抗原刺激bm12小鼠的CD4细胞，用IEk上的鸽细胞色素c肽刺激Vβ3/Vα11 TCR转基因小鼠的CD4细胞。两种转基因小鼠的T细胞均为初始表型，而正常小鼠含有10%-20%的记忆细胞。产生的效应CD8细胞群体L-选择素低、CD45RB高、CD44高。与能产生大量白细胞介素2（IL-2）的初始CD4细胞相比，SCID抗H-Y小鼠的初始CD8细胞在刺激后立即很少或不产生细胞因子。然而，这两种细胞群体在4-5天内都产生了主要效应细胞，这些效应细胞在再次刺激时能产生大量的多种细胞因子。CD8和CD4效应细胞在同种异体抗原或特异性抗原刺激下产生相似的细胞因子模式。如先前对CD4细胞的研究所示，初始CD8细胞刺激过程中存在的细胞因子会影响效应细胞的细胞因子分泌谱，尽管CD8效应细胞的分泌通常低于CD4效应细胞。单独用IL-2培养的CD8细胞主要产生干扰素γ（IFN-γ），不产生IL-4或IL-5，这与CD4细胞相似。用IFN-γ预处理可增加CD4效应细胞的IFN-γ分泌，但对CD8细胞几乎没有影响。相反，用IL-12预处理可使CD8效应细胞以及CD4效应细胞产生升高水平的IFN-γ，CD4和CD8细胞群体的水平相似。效应细胞生成过程中IL-4的存在促进了CD8和CD4细胞合成IL-4和IL-5，同时下调IFN-γ分泌。CD8细胞仅产生少量IL-4，比CD4细胞少100多倍，而诱导产生的IL-5水平显著，仅比CD4细胞低3-10倍。（摘要截选至400字）
