Despite large-scale T cell activation, only a minor subset of T cells responding in vitro to Actinobacillus actinomycetemcomitans differentiate into effector T cells.

Despite large-scale T cell activation, only a minor subset of T cells responding in vitro to Actinobacillus actinomycetemcomitans differentiate into effector T cells.
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尽管大规模 T 细胞激活,但只有一小部分 T 细胞在体外对伴放线放线杆菌做出反应,分化为效应 T 细胞。

DOI:
10.1034/j.1600-0765.2000.035003127.x
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发表时间:
2000
影响因子:
3.5
通讯作者:
Kreutzer,DL
Kreutzer,DL
中科院分区:
医学3区
文献类型:
--
作者:
Zadeh,HH;Tanavoli,S;Haines,DD;Kreutzer,DL

文献摘要

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我们实验室最近的研究表明,放线菌具有强大的T细胞刺激作用,激活了所有T细胞的一半以上。然而,由于这些活化T细胞的命运尚不清楚,本研究试图确定是否所有这些T细胞都分化为效应细胞。为此,T细胞细胞因子(IL‐2,IFN‐γ, IL‐4和IL‐10)的细胞内表达对a的响应。流式细胞术测定放线菌数量。结果显示细胞因子的表达呈时间依赖性增加,大多数在24-48 h达到峰值水平。48 h时,表达每种细胞因子的T细胞比例如下:IL‐2(1.7%±0.3),IFN‐γ(1.8%±0.5),IL‐4(1.0%±0.2)和IL‐10(1.5%±0.5)。这些数据表明,只有2-5%的T细胞受到a的刺激。放线菌不表达任何T细胞因子。在缺乏细胞因子表达的情况下,大规模T细胞活化的发现表明,T细胞的活化是对a的反应。actinomycetemcomitansis不完整。为了研究这种现象,我们用a培养外周血单核细胞(PBMC)。放线菌孵育24小时,然后用免疫磁分离对活化的(CD69+)细胞进行分选,并用12 -肉豆酸酯13 -醋酸酯(PMA)和离子霉素进行再刺激。结果表明,近90%的T细胞对进一步的再刺激无反应。对这种无应答性的可能解释是在应答的T细胞中诱导了克隆能。为了确定刺激对特定细胞因子的可能的优先效应,T细胞对a的反应中每种细胞因子的表达。将放线菌组与PMA+离子霉素刺激达到的最大水平进行比较。结果显示,IL - 2+和IFN - γ+T细胞的数量对a有反应。PMA+离子霉素组放线菌发生率在2% - 7%之间。相反,在PMA+离子霉素刺激后,表达IL - 4或IL - 10的T细胞比例在35%至90%之间。因此,一个。放线菌似乎更倾向于诱导T细胞
Recent studies in our laboratory have demonstrated thatActinobacillus actinomycetemcomitanshas a potent T cell stimulatory effect, activating more than half of all T cells. However, since the fate of these activated T cells was not known, the present study sought to determine whether all of these T cells differentiate into effector cells. To that end, the intracellular expression of T cell cytokines (IL‐2, IFN‐γ, IL‐4 and IL‐10) in response toA. actinomycetemcomitanswas determined by flow cytometry. Results demonstrated a time‐dependent increase in the expression of the cytokines, most reaching peak levels at 24–48 h. At 48 h, the proportion of T cells expressing each of the cytokines were as follows: IL‐2 (1.7%±0.3), IFN‐γ(1.8%±0.5), IL‐4 (1.0%±0.2) and IL‐10 (1.5%±0.5). These data indicated that only 2–5% of all T cells stimulated withA. actinomycetemcomitansexpressed any T cell cytokines. The finding of large‐scale T cell activation in the absence of cytokine expression suggests that the activation of T cells in response toA. actinomycetemcomitansis incomplete. To investigate this phenomenon, peripheral blood mononuclear cells (PBMC) were cultured withA. actinomycetemcomitansfor 24 h followed by sorting of the activated (CD69+) cells by immunomagnetic separation and restimulation with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. Results demonstrated that nearly 90% of the T cells were unresponsive to further restimulation. A possible explanation for this unresponsiveness is the induction of clonal anergy among the responding T cells. To determine possible preferential effects of the stimulation on specific cytokines, the expression of each cytokine among T cells responding toA. actinomycetemcomitanswas compared to the maximum levels achieved by PMA+ionomycin stimulation. Results showed that number of IL‐2+and IFN‐γ+T cells observed in response toA. actinomycetemcomitanswere between 2% and 7% of those seen in response to PMA+ionomycin. Conversely, the proportions of T cells expressing IL‐4 or IL‐10 were between 35% and 90% of those following stimulation with PMA+ionomycin. Hence,A. actinomycetemcomitansappears to more preferentially induce T cells