Chemokine expression by intraepithelial gamma delta T cells. Implications for the recruitment of inflammatory cells to damaged epithelia.
Chemokine expression by intraepithelial gamma delta T cells. Implications for the recruitment of inflammatory cells to damaged epithelia.
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DOI：
10.4049/jimmunol.157.3.985
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发表时间：
1996-08
影响因子：
4.4
通讯作者：
R. Boismenu;L. Feng;Y. Xia;J. Chang;W. Havran
中科院分区：
文献类型：
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作者：
R. Boismenu;L. Feng;Y. Xia;J. Chang;W. Havran
表达γ - δ TCR的T细胞可能已经进化到以不同的方式识别Ag，并且比具有α - β TCR的T细胞具有更广泛的功能。在这项研究中，我们验证了树突状表皮T细胞（DETC）携带不变的V γ 3V δ 1 TCR可能能够通过分泌特异性趋化因子来指示外周α β T细胞向表皮的迁移。DETC 7-17细胞可诱导巨噬细胞炎症蛋白(MIP)-1 α、MIP-1 β、RANTES和淋巴趋化素的表达，而单核细胞趋化蛋白(MCP)-1的mRNA未检测到。引人注目的是，淋巴趋化素是活化的DETC 7-17细胞产生的最丰富的趋化因子。激活的DETC原代培养物也产生大量的淋巴趋化素mRNA。同样，具有γ δ TCR的新鲜分离和激活的肠上皮内T细胞（i-IEL）表达高水平的淋巴素mRNA。相比之下，活化的脾脏γ δ T细胞中存在低基础水平的淋巴趋动素mRNA。受刺激DETC 7-17细胞培养上清液诱导的CD8+ T细胞的迁移在中和抗淋巴趋化素抗血清的存在下强烈减少，在较小程度上中和抗mip -1 α、抗mip -1 β或抗rantes抗血清。Western blot分析直接证实了活化DETC 7-17培养的上清中存在淋巴素。这些观察结果与伽马δ IEL在维持上皮稳态中发挥积极的多方面作用的模型一致。
T cells expressing gamma delta TCR may have evolved to recognize Ag in a different manner as well as perform a broader set of functions than T cells with alpha beta TCR. In this study, we tested the hypothesis that dendritic epidermal T cells (DETC) bearing the invariant V gamma 3V delta 1 TCR may be able to signal the migration of peripheral alpha beta T cells to the epidermis by secreting specific chemokines. Expression of macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, RANTES, and lymphotactin was inducible in DETC 7-17 cells, whereas mRNA for monocyte chemoattractant protein (MCP)-1 could not be detected. Strikingly, lymphotactin was the most abundant chemokine produced by activated DETC 7-17 cells. Activated primary DETC cultures also produced copious amounts of lymphotactin mRNA. Similarly, freshly isolated and activated intestinal intraepithelial T cells (i-IEL) with gamma delta TCR expressed high levels of lymphotactin mRNA. In contrast, lymphotactin mRNA was present in activated spleen gamma delta T cells at low basal levels. Migration of CD8+ T cells induced by culture supernatants from stimulated DETC 7-17 cells was strongly reduced in the presence of a neutralizing anti-lymphotactin antiserum and to a lesser extent by neutralizing anti-MIP-1 alpha, anti-MIP-1 beta, or anti-RANTES antiserum. The presence of lymphotactin in supernatants from activated DETC 7-17 cultures was directly demonstrated by Western blot analysis. These observations are consistent with a model in which gamma delta IEL play an active multi-faceted role in the maintenance of epithelia homeostasis.