Inhibitory effect of HTLV-1 infection on the production of B-cell activating factors in established follicular dendritic cell-like cells.

Inhibitory effect of HTLV-1 infection on the production of B-cell activating factors in established follicular dendritic cell-like cells.
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HTLV-1感染对已建立的滤泡树突状细胞样细胞中B细胞活化因子产生的抑制作用。

DOI:
10.1002/iid3.432
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发表时间:
2021-09
期刊:
Immunity, inflammation and disease
影响因子:
--
通讯作者:
Kawakami A
Kawakami A
中科院分区:
其他
文献类型:
--
作者:
Takatani A;Nakamura H;Furukawa K;Endo Y;Umeda M;Shimizu T;Nishihata SY;Kitaoka K;Nakamura T;Kawakami A

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人类T细胞白血病病毒1型(HTLV-1)抗体阳性干燥综合征(SS)患者唇腺异位生发中心出现频率低,提示HTLV-1对滤泡树突状细胞(FDCs)有一定作用。我们使用流式细胞术、免疫荧光和酶联免疫吸附试验(ELISA)来研究HTLV-1对从人扁桃体切除的FDC样细胞产生的B细胞激活因子的直接影响。用双抗体夹心法检测HTLV-1阳性SS患者和HTLV-1阴性SS患者血清中B细胞活化因子(BAFF)和C-X-C基序配体(CXCL)13的浓度。在分离的31份标本中,有22份具有FDCs的形态特征。培养第2天的标本表达CD14、CD23、CD40、细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1。2周后,12例标本表达ICAM-1、FDC和成纤维细胞标志。无论刺激与否,BAFF和CXCL13在细胞内均呈结构性表达。与HTLV-1感染的T细胞株HCT-5或MT-2直接共培养后,FDC样细胞表面BAFF和CXCL13的表达减少,这与有茎状改变的HCT-5和MT-2细胞的数量增加以及HTLV-1 Gag蛋白表达的减少一致。干扰素可上调培养上清液中BAFF(而不是CXCL13)的浓度,在HCT-5或MT-2存在下呈下降趋势。HTLV-1阳性SS患者血清BAFF和CXCL13浓度低于HTLV-1血清阴性SS患者。HTLV-1部分抑制FDC样细胞BAFF和CXCL13的表达。加入干扰素可上调B细胞活化因子(BAFF)的表达。虽然加入人T细胞白血病病毒1型感染细胞株HCT-5和MT-2可抑制BAFF的表达,但加入对照细胞株MOLT-4不能抑制BAFF的表达。
The low frequency of ectopic germinal center in labial salivary glands of patients with human T‐cell leukemia virus type 1 (HTLV‐1) antibody‐positive Sjögren's syndrome (SS) suggests that HTLV‐1 has some effects on follicular dendritic cells (FDCs). We used flow cytometry, immunofluorescence, and enzyme‐linked immunosorbent assays (ELISAs) to investigate the direct effect of HTLV‐1 on B‐cell activating factors produced by established FDC like cells obtained from excised human tonsils. We then measured the serum B‐cell activating factor (BAFF) and C‐X‐C motif ligand (CXCL) 13 concentrations of the HTLV‐1‐seropositive SS patients and the HTLV‐1‐seronegative SS patients by ELISA. Among the 31 isolated specimens, 22 showed morphological characteristics of FDCs. Day 2‐cultured specimens showed expressions of CD14, CD23, CD40, intracellular adhesion molecule‐1 (ICAM‐1), and vascular cell adhesion molecule‐1. After 2 weeks, 12 of these specimens expressed ICAM‐1, FDC, and fibroblast cell marker. Intracellular BAFF and CXCL13 were constitutively expressed regardless of stimulation. After direct coculture with the HTLV‐1‐infected T‐cell line HCT‐5 or MT‐2, the BAFF and CXCL13 expressions on the FDC‐like cells were decreased in accord with the increased number of HCT‐5 and MT‐2 cells with styliform change and without HTLV‐1 Gag protein expression. Interferons upregulated the concentration of BAFF (but not CXCL13) in the culture supernatant, which showed a declining trend under the presence of HCT‐5 or MT‐2. The serum concentrations of BAFF and CXCL13 in the HTLV‐1‐seropositive SS patients were lower than those of the HTLV‐1 seronegative SS patients. HTLV‐1 partially inhibited the BAFF and CXCL13 expressions of established FDC‐like cells. Expression of B‐cell activating factor (BAFF) was upregulated by addition of interferons. Although BAFF expression was inhibited by addition of human T‐cell leukemia virus type 1 infected cell line, HCT‐5 and MT‐2, the level was not inhibited by addition of control cell line, MOLT‐4.
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