Preferential production of interferon-γ by CD4+ T cells expressing the homing receptor integrin α4/β7
Preferential production of interferon-γ by CD4+ T cells expressing the homing receptor integrin α4/β7
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DOI：
10.1046/j.0019-2805.2001.01234.x
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发表时间：
2001-06-01
期刊：
影响因子：
6.4
通讯作者：
Erle, DJ
中科院分区：
文献类型：
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作者：
Abramson, O;Qiu, SQ;Erle, DJ
最近的研究表明，辅助性T细胞1型(Th1)和2型(Th2)淋巴细胞表达的控制T细胞迁移的分子不同，包括黏附分子和趋化因子受体。我们研究了细胞因子的产生与T细胞上归巢受体整合素α(4)/β(7)表达的关系。我们首先分析了在佛波酯(PMA)和离子霉素短暂(4小时)刺激后，人类CD4(+)CD45RA(-)记忆/效应T细胞产生的细胞因子。在所有六个受试者中，α(4)/β(高)(7)CD4(+)T细胞比α(4)/β(-)(7)CD4(+)T细胞更有可能产生Th1细胞因子干扰素-伽马(IFN-Gamma)。相反，Th2细胞因子IL-4在α(4)/β(高)(7)和α(4)/β(-)(7)CD4(+)T细胞上的产生相似。此外，我们还发现，黏附于α(4)/β(7)配体粘膜寻址细胞黏附分子-1(MAdCAM-1)的人CD4(+)CD45RA-T细胞比未黏附的细胞具有更强的产生干扰素-γ的能力，这表明α(4)/β(7)的表达与干扰素-γ的产生之间的关联具有功能意义。这些结果表明，在Th1促进条件下的初级激活可能有利于α(4)/β(7)的表达。我们直接研究了这种可能性，发现在Th1促进条件下激活的初始小鼠CD4+T细胞比在Th2促进条件下激活的细胞表达更高水平的α(4)/β(7)。当MAdCAM-1在肠道或其他部位炎症部位表达时，α(4)/β(7)表达与CD4(+)T细胞产生的干扰素-γ之间的关联可能有助于确定细胞因子的平衡。
Recent studies indicate that T helper type 1 (Th1) and 2 (Th2) lymphocytes differ in their expression of molecules that control T-cell migration, including adhesion molecules and chemokine receptors. We investigated the relationship between cytokine production and expression of the homing receptor integrin alpha (4)/beta (7) on T cells. We began by analysing cytokine production by human CD4(+) CD45RA(-) memory/effector T cells following brief (4 hr) stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. alpha (4)/beta (high)(7) CD4(+) T cells were more likely to produce the Th1 cytokine interferon-gamma (IFN-gamma) than were alpha (4)/beta (-)(7) CD4(+) T cells in all six subjects studied. In contrast, production of the Th2 cytokine interleukin-4 (IL-4) was similar on alpha (4)/beta (high)(7) and alpha (4)/ beta (-)(7) CD4(+) T cells. In addition, we found that human CD4(+) CD45RA- T cells that adhered to the alpha (4)/beta (7) ligand mucosal addressin cell adhesion molecule-1 (MAdCAM-1) had a greater capacity to produce IFN-gamma than did non-adherent cells, suggesting that the association between alpha (4)/beta (7) expression and IFN-gamma production has functional significance. These results suggested that primary activation under Th1-promoting conditions might favour expression of alpha (4)/beta (7) we directly examined this possibility, and found that naive murine CD4+ T cells activated under Th1-promoting conditions expressed higher levels of alpha (4)/beta (7) compared to cells activated under Th2-promoting conditions. The association between alpha (4)/beta (7) expression and IFN-gamma production by CD4(+) T cells may help to determine the cytokine balance when MAdCAM-1 is expressed at sites of inflammation in the intestine or elsewhere.