Importance of IFN-γ-mediated expression of endothelial VCAM-1 on recruitment of CD8+ T cells into the brain during chronic infection with Toxoplasma gondii
Importance of IFN-γ-mediated expression of endothelial VCAM-1 on recruitment of CD8+ T cells into the brain during chronic infection with Toxoplasma gondii
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DOI：
10.1089/jir.2006.0154
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发表时间：
2007-04-01
影响因子：
2.3
通讯作者：
Suzuki, Yasuhiro
中科院分区：
文献类型：
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作者：
Wang, Xisheng;Michie, Sara A.;Suzuki, Yasuhiro
干扰素- γ (ifn - γ)对于预防大脑中弓形虫慢性感染的再激活至关重要。我们研究了ifn - γ敲除（ifn - γ(-/-)）和野生型（WT）小鼠慢性弓形虫感染期间，ifn - γ对淋巴细胞和内皮粘附分子表达以及T细胞向脑募集的作用。尽管在感染后WT和ifn - γ(-/-)小鼠中表达细胞间粘附分子-1（ICAM-1）和血管细胞粘附分子-1（VCAM-1）的脑血管数量增加，但感染WT的大脑中VCAM-1（+）血管数量多于感染ifn - γ(-/-)小鼠；相比之下，不同菌株间ICAM-1（+）血管的数量没有差异。我们没有在任何大脑中检测到内皮细胞e -选择素、p -选择素、MAdCAM-1或PNAd。与WT小鼠相比，感染ifn - γ(-/-)的小鼠招募的CD8(+) T细胞明显减少。用重组ifn - γ治疗感染的ifn - γ(-/-)小鼠，恢复了VCAM-1在其脑血管上的表达和CD8(+) T细胞进入其大脑的募集，证实了该细胞因子对上调VCAM-1表达和CD8(+) T细胞运输的重要性。在受感染的WT和ifn - γ(-/-)动物中，几乎所有的脑CD8(+) T细胞都是淋巴细胞功能相关抗原-1 (LFA-1)（高）、CD44（高）和CD62L（负），大约38%是α 4 β 1整合素（+）。在免疫脾细胞过继转移中，用抗α 4整合素的单克隆抗体（mAb）预处理细胞可显著抑制慢性感染WT小鼠的CD8(+) T细胞向大脑募集。这些结果表明，在弓形虫感染的慢性阶段，ifn - γ诱导内皮细胞VCAM-1的表达及其与CD8(+) T细胞上α 4 β 1整合素的结合对于T细胞募集到大脑是重要的，尽管LFA-1/ICAM-1相互作用可能也参与了这一过程。
Interferon-gamma ( IFN-gamma) is essential for preventing reactivation of chronic infection with Toxoplasma gondii in the brain. We examined the role of IFN-gamma on lymphocyte and endothelial adhesion molecule expression and T cell recruitment into the brain during chronic infection with T. gondii in IFN-gamma knockout ( IFN-gamma(-/-)) and wild-type ( WT) mice. Although the number of cerebral vessels expressing intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) increased in both WT and IFN-gamma(-/-) mice following infection, there were more VCAM-1(+) vessels in brains of infected WT than of infected IFN-gamma(-/-) mice; in contrast, numbers of ICAM-1(+) vessels did not differ between strains. We did not detect endothelial E-selectin, P-selectin, MAdCAM-1, or PNAd in any of the brains. Significantly fewer CD8(+) T cells were recruited into brains of infected IFN-gamma(-/-) than WT mice. Treatment of infected IFN-gamma(-/-) mice with recombinant IFN-gamma restored the expression of VCAM-1 on their cerebral vessels and recruitment of CD8(+) T cells into their brains, confirming an importance of this cytokine for upregulation of VCAM-1 expression and CD8(+) T cell trafficking. In infected WT and IFN-gamma(-/-) animals, almost all cerebral CD8(+) T cells were lymphocyte function-associated antigen-1 (LFA-1)(high), CD44(high), and CD62L(neg), and approximately 38% were alpha 4 beta 1 integrin(+). In adoptive transfer of immune spleen cells, pretreatment of the cells with a monoclonal antibody (mAb) against alpha 4 integrin markedly inhibited recruitment of CD8(+) T cells into the brain of chronically infected WT mice. These results indicate that IFN-gamma-induced expression of endothelial VCAM-1 and its binding to alpha 4 beta 1 integrin on CD8(+) T cells is important for recruitment of the T cells into the brain during the chronic stage of T. gondii infection, although LFA-1/ICAM-1 interaction may also be involved in this process.