Interaction between human lung fibroblasts and T-lymphocytes prevents activation of CD4+ cells.
Interaction between human lung fibroblasts and T-lymphocytes prevents activation of CD4+ cells.
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DOI：
10.1186/1465-9921-6-103
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发表时间：
2005-09-13
影响因子：
5.8
通讯作者：
Crimi N
中科院分区：
文献类型：
--
作者：
Vancheri C;Mastruzzo C;Trovato-Salinaro E;Gili E;Lo Furno D;Pistorio MP;Caruso M;La Rosa C;Crimi C;Failla M;Crimi N
T淋巴细胞在一些慢性肺部炎症性疾病中起重要作用。在这项研究中，我们提供的证据表明，人肺成纤维细胞能够相互作用的T淋巴细胞，导致功能显着的反应，T细胞和成纤维细胞。将人肺成纤维细胞与PMA-离子霉素活化的T-CD 4淋巴细胞共培养36小时。通过流式细胞术和RT-PCR评价与成纤维细胞和淋巴细胞活化相关的表面和细胞内蛋白表达。MTT法检测T淋巴细胞对刀豆球蛋白A的增殖反应。在肺成纤维细胞中，活化的淋巴细胞促进环氧合酶-2和ICAM-1表达的增加，以平均荧光强度（MFI）表示，分别从5.4 ± 0.9和0.7 ± 0.15增加至9.1 ± 1.5和38.6 ± 7.8。成纤维细胞反过来诱导活化淋巴细胞中CD 69、LFA-1和CD 28以及静息淋巴细胞中CD 3的转录和蛋白表达的显著降低。在活化的T淋巴细胞中，LFA-1、CD 28和CD 69表达分别为16.6 ± 0.7、18.9 ± 1.9和6.6 ± 1.3，并且被成纤维细胞显著降低至9.4 ± 0.7、9.4 ± 1.4和3.5 ± 1.0。静息淋巴细胞中的CD 3表达为11.9 ± 1.4，成纤维细胞显著降低至6.4 ± 1.1。在T淋巴细胞中评价细胞内细胞因子TNF-α和IL-10。与成纤维细胞共孵育将TNF-α阳性淋巴细胞的数量从54.4% ± 6.12减少到30.8 ± 2.8，而IL-10阳性细胞不受影响。最后，与成纤维细胞共培养显著降低了T淋巴细胞的ConA增殖反应，以MTT吸光度测量，从0.24 ± 0.02 nm降至0.16 ± 0.02 nm。有趣的是，虽然成纤维细胞的活化是由可溶性因子介导的，但已证明ICAM-1介导的同源相互作用负责LFA-1、CD 28和CD 69的调节。这项研究的结果表明，成纤维细胞在免疫反应的局部调节中发挥作用，能够调节招募到炎症部位的细胞的效应子功能。
T lymphocytes are demonstrated to play an important role in several chronic pulmonary inflammatory diseases. In this study we provide evidence that human lung fibroblasts are capable of mutually interacting with T-lymphocytes leading to functionally significant responses by T-cells and fibroblasts. Human lung fibroblast were co-cultured with PMA-ionomycin activated T-CD4 lymphocytes for 36 hours. Surface as well as intracellular proteins expression, relevant to fibroblasts and lymphocytes activation, were evaluated by means of flow cytometry and RT-PCR. Proliferative responses of T lymphocytes to concanavalin A were evaluated by the MTT assay. In lung fibroblasts, activated lymphocytes promote an increase of expression of cyclooxygenase-2 and ICAM-1, expressed as mean fluorescence intensity (MFI), from 5.4 ± 0.9 and 0.7 ± 0.15 to 9.1 ± 1.5 and 38.6 ± 7.8, respectively. Fibroblasts, in turn, induce a significant reduction of transcription and protein expression of CD69, LFA-1 and CD28 in activated lymphocytes and CD3 in resting lymphocytes. In activated T lymphocytes, LFA-1, CD28 and CD69 expression was 16.6 ± 0.7, 18.9 ± 1.9 and 6.6 ± 1.3, respectively, and was significantly reduced by fibroblasts to 9.4 ± 0.7, 9.4 ± 1.4 and 3.5 ± 1.0. CD3 expression in resting lymphocytes was 11.9 ± 1.4 and was significantly reduced by fibroblasts to 6.4 ± 1.1. Intracellular cytokines, TNF-alpha and IL-10, were evaluated in T lymphocytes. Co-incubation with fibroblasts reduced the number of TNF-alpha positive lymphocytes from 54,4% ± 6.12 to 30.8 ± 2.8, while IL-10 positive cells were unaffected. Finally, co-culture with fibroblasts significantly reduced Con A proliferative response of T lymphocytes, measured as MTT absorbance, from 0.24 ± 0.02 nm to 0.16 ± 0.02 nm. Interestingly, while the activation of fibroblasts is mediated by a soluble factor, a cognate interaction ICAM-1 mediated was demonstrated to be responsible for the modulation of LFA-1, CD28 and CD69. Findings from this study suggest that fibroblasts play a role in the local regulation of the immune response, being able to modulate effector functions of cells recruited into sites of inflammation.
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DOI：
10.1165/ajrcmb.10.5.8179910
发表时间：
1994-05-01
影响因子：
6.4
作者：
DENIS, M;BISSON, D
通讯作者：
BISSON, D
影响因子：
20.3
作者：
Hyde, H;Borthwick, NJ;Akbar, AN
通讯作者：
Akbar, AN
影响因子：
7.6
作者：
Murakami, S;Hino, E;Okada, H
通讯作者：
Okada, H
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N
影响因子：
15.9
作者：
Lentsch, AB;Shanley, TP;Ward, PA
通讯作者：
Ward, PA