A role for CD103 in the retention of CD4+CD25+ Treg and control of Leishmania major infection
A role for CD103 in the retention of CD4+CD25+ Treg and control of Leishmania major infection
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DOI：
10.4049/jimmunol.174.9.5444
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发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
Belkaid, Y
中科院分区：
文献类型：
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作者：
Suffia, I;Reckling, SK;Belkaid, Y
内源性调节性T细胞（T1 g）在控制针对自身或外来Ag的过度或错误定向的免疫应答中起核心作用。迄今为止，几乎没有数据可用于在需要调节的组织中参与T-reg的运输和保留的分子和信号的性质。在这里，我们表明，α（E）β（7）整合素的表达是必要的归巢在网站的主要利什曼原虫感染的T-reg。在稳态条件下或在L.主要感染表现为A.α（E）β（7）的链（CD 103）。缺乏CD 103的遗传易感BALB/c小鼠变得对感染具有抗性，这是一种与T-reg在感染部位保留的能力差相关的表型。当来自野生型小鼠的T-reg转移到CD 103（-/-）小鼠中时，这种易感表型可以恢复。通过使用针对CD 103的阻断Ab和从CD 103（-/-）小鼠纯化的T-reg的转移，进一步证明了CD 103在Treg保留中的中心作用。我们的研究结果强烈表明，这种分子是诱导和维持在T-reg后或之前，他们到达组织。此外，CD 103的表达和随后的T-reg在组织中的保留受到它们暴露于利什曼原虫抗原和它们遇到的APC的活化水平的高度调节。因此，CD 103通过控制T-reg保留，可以有助于利什曼原虫慢性感染的结果。
Endogenous regulatory T cells (T,,g) play a central role in the control of excessive or misdirected immune responses against self or foreign Ags. To date, virtually no data are available on the nature of the molecules and signals involved in the trafficking and retention of T-reg in tissues where regulation is required. Here, we show that expression of alpha(E)beta(7) integrin is necessary for the homing of T-reg at site of Leishmania major infection. The vast majority of T-reg present in the dermis at steady-state conditions or during L. major infection express the a. chain (CD103) of alpha(E)beta(7). Genetically susceptible BALB/c mice that lack CD103 become resistant to infection, a phenotype that is associated with a poor capacity of T-reg to be retained in the infected site. Such susceptible phenotype can be restored when T-reg from wild-type mice were transferred in CD103(-/-) mice. The central role of CD103 in Treg retention was further demonstrated by usage of blocking Abs against CD103 and the transfer of T-reg purified from CD103(-/-) mice. Our results strongly suggest that this molecule is induced and maintained on T-reg following or just prior to their arrival in tissues. Furthermore, the expression of CD103 and the subsequent retention of T-reg in tissues is highly regulated by their exposure to Leishmania Ag and the level of activation of the APCs they encounter. Thus, CD103, by controlling T-reg retention, can contribute to the outcome of chronic infection by Leishmania.