CD4+ and CD8+ T cell priming for contact hypersensitivity occurs independently of CD40-CD154 interactions
CD4+ and CD8+ T cell priming for contact hypersensitivity occurs independently of CD40-CD154 interactions
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DOI：
10.4049/jimmunol.166.4.2323
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发表时间：
2001-02-15
影响因子：
4.4
通讯作者：
Fairchild, RL
中科院分区：
文献类型：
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作者：
Gorbachev, AV;Heeger, PS;Fairchild, RL
对二氟苯(DNFB)产生接触超敏反应(CHS)的主要效应细胞是产生IFN-γ的CD8(+)T细胞，而CD4(+)T细胞调节反应的强度和持续时间。半抗原呈递朗格汉斯细胞 (hpLC) 在 CD8+ 和 CD4(+) T 细胞启动过程中对 CD40-CD154 参与的要求尚未明确，并在当前研究中进行了测试。在野生型和 CD154(-/-) 动物中也引发了类似的对 DNFB 的 CHS 反应。 CD154(-/-)小鼠的DNFB致敏引发了产生IFN-γ的CD8(+)T细胞和产生IL-4的CD4(+)T细胞。然而，在半抗原致敏期间给予的抗CD154 mAb MR1抑制半抗原特异性CD8(+)，但不抑制CD4(+)、T细胞发育和CHS对攻击的反应。 MR1 的 F(ab')(2) 未能抑制 CD8(+) T 细胞发育和 CHS 反应，表明抑制机制与 CD40-CD154 阻断不同。此外，抗CD154 mAb不会抑制CD4(+) T细胞耗尽的小鼠或CD4(-/-)小鼠中CD8(+) T细胞的发育和CHS反应。在体外增殖测定中，来自在 DNFB 致敏过程中使用抗 CD154 mAb 处理的小鼠的 hpLC 对半抗原引发的 T 细胞的刺激性低于来自对照小鼠或在施用抗 CD154 mAb 之前去除 CD4(+) T 细胞的小鼠的 hpLC。这些结果表明，产生IFN-γ的CD8(+)T细胞的发育和CHS反应不依赖于CD40-CD154相互作用。这项研究提出了一种抗CD154 mAb介导的抑制CD8(+) T细胞发育的新机制，其中抗CD154 mAb通过CD4(+) T细胞间接发挥作用，削弱hpLC启动CD8(+) T细胞的能力。
The primary effector cells of contact hypersensitivity (CHS) responses to dintrofluorobenzene (DNFB) are IFN-gamma -producing CD8(+) T cells, whereas CD4(+) T cells regulate the magnitude and duration of the response. The requirement for CD40-CD154 engagement during CD8+ and CD4(+) T cell priming by hapten-presenting Langerhans cells (hpLC) is undefined and was tested in the current study. Similar CHS responses to DNFB were elicited in wild-type and CD154(-/-) animals. DNFB sensitization of CD154(-/-) mice primed IFN-gamma -producing CD8(+) T cells and IL-4-producing CD4(+) T cells. However, anti-CD154 mAb MR1 given during hapten sensitization inhibited hapten-specific CD8(+), but not CD4(+), T cell development and the CHS response to challenge. F(ab')(2) of MR1 failed to inhibit CD8(+) T cell development and the CHS response suggesting that the mechanism of inhibition is distinct from that of CD40-CD154 blockade. Furthermore, anti-CD154 mAb did not inhibit CD8(+) T cell development and CHS responses in mice depleted of CD4(+) T cells or in CD4(-/-) mice. During in vitro proliferation assays, hpLC from mice treated with anti-CD154 mAb during DNFB sensitization were less stimulatory for hapten-primed T cells than hpLC from either control mice or mice depleted of CD4(+) T cells before anti-CD154 mAb administration. These results demonstrate that development of IFN-gamma -producing CD8(+) T cells and the CHS response are not dependent on CD40-CD154 interactions. This study proposes a novel mechanism of anti-CD154 mAb-mediated inhibition of CD8(+) T cell development where anti-CD154 mAb acts indirectly through CD4(+) T cells to impair the ability of hpLC to prime CD8(+) T cells.