Interleukin-21 inhibits dendritic cell-mediated t cell activation and induction of contact hypersensitivity in vivo
Interleukin-21 inhibits dendritic cell-mediated t cell activation and induction of contact hypersensitivity in vivo
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DOI：
10.1046/j.1523-1747.2003.12603.x
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发表时间：
2003-12-01
影响因子：
6.5
通讯作者：
Rückert, R
中科院分区：
文献类型：
--
作者：
Brandt, K;Bulfone-Paus, S;Rückert, R
白细胞介素（IL）-21是一种新发现的细胞因子，由活化的T细胞产生，与IL-4和IL-15具有结构同源性。我们在此分析了IL-21在体内树突状细胞（DC）诱导的、T细胞介导的接触超敏反应（CHS）中以及在体外对T细胞活化和非特异性混合淋巴细胞反应的作用。通过PCR，我们证明了在DC中特异性IL-21受体和共同γ链的组成型表达，它们一起能够介导IL-21信号传导。体外产生的DC与IL-21的短时间孵育显著降低了它们诱导抗原特异性CD 8 + T细胞增殖的潜力。有趣的是，在注射前将这些DC与IL-21孵育2小时完全抑制了这些DC在体内诱导半抗原荧光素5-异硫氰酸酯的CHS反应的潜力。用IL-21处理的DC注射的小鼠在2周后重复注射非IL-21处理的DC后甚至未能建立CHS应答，这表明抗原特异性无应答性可由IL-21处理的DC诱导。我们的数据表明，IL-21是一种新的DC-T细胞相互作用的调节剂，具有诱导DC介导的抗原特异性耐受的潜力。
Interleukin (IL)-21 is a newly described cytokine that is produced by activated T cells and displays structural homology to IL-4 and IL-15. We here analyzed the role of IL-21 in dendritic cell (DC)-induced, T cell-mediated contact hypersensitivity (CHS) in vivo and on T cell activation and unspecific mixed lymphocyte reaction in vitro. By PCR, we demonstrate here constitutive expression of the specific IL-21 receptor and the common gamma-chain in DC, which together are able to mediate IL-21 signaling. Short-time incubation of in vitro generated DC with IL-21 significantly reduced their potential to induce an antigen-specific CD8+ T cell proliferation. Interestingly, 2h incubation of these DC with IL-21 before injection completely inhibited the potential of these DC to induce a CHS reaction to the hapten fluorescein 5-isothiocyanate in vivo. Mice injected with IL-21-treated DC even failed to mount a CHS response after repetitive injection of non-IL-21-treated DC 2 weeks later, suggesting that an antigen-specific unresponsiveness can be induced by IL-21-treated DC. Our data demonstrate that IL-21 is a new modulator of DC-T cell interaction with the potential to induce DC-mediated antigen-specific tolerance.