Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles.
Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles.
复制标题
DOI：
10.1084/jem.180.5.1715
复制
发表时间：
1994-11-01
影响因子：
15.3
通讯作者：
Dutton, Richard W.
中科院分区：
文献类型：
--
作者：
Croft, Michael;Carter, Laura;Swain, Susan L.;Dutton, Richard W.
我们从初始CD8 T细胞针对抗原产生了初级效应细胞群，并确定了它们在再次刺激时的细胞因子分泌模式。研究了外源性因素对效应细胞产生的影响，并与在可比条件下产生的抗原特异性CD4效应细胞的反应进行了比较。来自bm1小鼠的CD8细胞由携带同种异体I类分子的C57BL/6（B6）抗原呈递细胞（APC）刺激，来自雌性重症联合免疫缺陷（SCID）B6小鼠且对Db上的H - Y有识别能力的T细胞受体α/β（TCR - α/β）转基因的CD8细胞由雄性小鼠的APC刺激。同时，来自bm12小鼠的CD4细胞由同种异体抗原刺激，来自Vβ3/Vα11 TCR转基因小鼠的CD4细胞由鸽细胞色素c的一个肽段在IEk上刺激。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细胞群为L - 选择素低、CD45RB高和CD44高。与初始CD4细胞产生大量白细胞介素2（IL - 2）相反，来自SCID抗 - H - Y小鼠的初始CD8细胞在刺激时几乎不产生细胞因子。然而，这两种细胞群在4 - 5天内都产生了初级效应细胞，再次刺激时会产生大量多种细胞因子。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细胞所示，初始CD8刺激过程中存在的细胞因子影响了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预刺激增加了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预刺激产生了CD8效应细胞以及CD4效应细胞，两者都产生更高量的IFN - γ，且CD4和CD8细胞群的水平相似。效应细胞产生过程中IL - 4的存在促进了CD8和CD4细胞的IL - 4和IL - 5合成，同时下调了IFN - γ分泌。CD8细胞仅产生少量IL - 4，比CD4细胞少100倍以上，而诱导产生的IL - 5水平显著，仅比CD4细胞低3 - 10倍。（摘要截断于400字）
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)
登录
查看更多内容
影响因子：
5.4
作者：
HORVAT, B;LOUKIDES, JA;FLOOD, PM
通讯作者：
FLOOD, PM
影响因子：
56.9
作者：
SALGAME, P;ABRAMS, JS;BLOOM, BR
通讯作者：
BLOOM, BR
DOI：
10.1073/pnas.89.13.6065
发表时间：
1992-07-01
影响因子：
11.1
作者：
HSIEH, CS;HEIMBERGER, AB;MURPHY, KM
通讯作者：
MURPHY, KM
影响因子：
--
作者：
Gasser, D L;Silvers, W K
通讯作者：
Silvers, W K
影响因子：
64.8
作者：
MORRIS, AG;LIN, YL;ASKONAS, BA
通讯作者：
ASKONAS, BA