Characterization and functional properties of gastric tissue-resident memory T cells from children, adults, and the elderly.

Characterization and functional properties of gastric tissue-resident memory T cells from children, adults, and the elderly.
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来自儿童,成人和老年人的胃组织居住记忆T细胞的表征和功能特性。

DOI:
10.3389/fimmu.2014.00294
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发表时间:
2014
影响因子:
7.3
通讯作者:
Sztein MB
Sztein MB
中科院分区:
医学2区
文献类型:
--
作者:
Booth JS;Toapanta FR;Salerno-Goncalves R;Patil S;Kader HA;Safta AM;Czinn SJ;Greenwald BD;Sztein MB

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T细胞是胃中保护性免疫的主要协调者;然而,关于胃T亚群的存在和功能的有限信息主要是由于难以从人胃活检中回收大量的活细胞。为了克服这一缺点,我们优化了细胞分离方法,从胃活检中获得大量的活固有层单核细胞(LPMC)。在胃LPMC中鉴定经典记忆T亚群,并使用优化的14色流式细胞术面板将其与从儿童、成人和老年人获得的外周血单核细胞(PBMC)进行比较。在所有年龄组的胃LPMC CD 4+和CD 8 + T细胞中观察到显性效应记忆T(TEM)表型。然后,我们通过评估CD 103和CD 69的表达来评估这些细胞是否代表胃组织驻留记忆T(TRM)细胞的群体。绝大多数胃LPMC CD 8 + T细胞共表达CD 103/CD 69(>70%)或仅表达CD 103(~20%)。胃LPMC CD 4 + T细胞也共表达CD 103/CD 69(>35%)或表达这些标志物中的至少一种。因此,胃LPMC的CD 8+和CD 4 + T细胞具有TRM细胞的特征。胃CD 8+和CD 4 + TRM细胞在刺激后产生多种细胞因子(IFN-γ、IL-2、TNF-α、IL-17 A、MIP-1β)并上调CD 107 a。然而,显着的差异,观察到他们的细胞因子和多细胞因子的档案相比,他们的PBMC TEM同行。此外,胃CD 8 + TRM和CD 4 + TRM细胞在各年龄组的频率、活化易感性和细胞因子/多细胞因子产生特征方面存在差异。最值得注意的是,儿童的胃TRM细胞对刺激的反应不同于成人或老年人的胃TRM细胞。总之,我们证明了胃TRM的存在,表现出不同的功能特点,在儿童,成人和老年人。
T cells are the main orchestrators of protective immunity in the stomach; however, limited information on the presence and function of the gastric T subsets is available mainly due to the difficulty in recovering high numbers of viable cells from human gastric biopsies. To overcome this shortcoming we optimized a cell isolation method that yielded high numbers of viable lamina propria mononuclear cells (LPMC) from gastric biopsies. Classic memory T subsets were identified in gastric LPMC and compared to peripheral blood mononuclear cells (PBMC) obtained from children, adults, and the elderly using an optimized 14 color flow cytometry panel. A dominant effector memory T (TEM) phenotype was observed in gastric LPMC CD4+ and CD8+ T cells in all age groups. We then evaluated whether these cells represented a population of gastric tissue-resident memory T (TRM) cells by assessing expression of CD103 and CD69. The vast majority of gastric LPMC CD8+ T cells either co-expressed CD103/CD69 (>70%) or expressed CD103 alone (~20%). Gastric LPMC CD4+ T cells also either co-expressed CD103/CD69 (>35%) or expressed at least one of these markers. Thus, gastric LPMC CD8+ and CD4+ T cells had the characteristics of TRM cells. Gastric CD8+ and CD4+ TRM cells produced multiple cytokines (IFN-γ, IL-2, TNF-α, IL-17A, MIP-1β) and up-regulated CD107a upon stimulation. However, marked differences were observed in their cytokine and multi-cytokine profiles when compared to their PBMC TEM counterparts. Furthermore, gastric CD8+ TRM and CD4+ TRM cells demonstrated differences in the frequency, susceptibility to activation, and cytokine/multi-cytokine production profiles among the age groups. Most notably, children’s gastric TRM cells responded differently to stimuli than gastric TRM cells from adults or the elderly. In conclusion, we demonstrate the presence of gastric TRM, which exhibit diverse functional characteristics in children, adults, and the elderly.
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