Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor site by crosspresenting APCs
Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor site by crosspresenting APCs
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DOI：
10.1016/j.immuni.2004.12.008
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发表时间：
2005-02-01
期刊：
影响因子：
32.4
通讯作者：
Walker, PR
中科院分区：
文献类型：
--
作者：
Calzascia, T;Masson, F;Walker, PR
组织特异性归巢分子的表达将经历过抗原的 T 细胞引导至特定的外周组织。在使用针对皮肤和肠道的可溶性抗原的研究中，区域淋巴组织内的抗原呈递细胞（APC）被认为负责印记归巢表型。这是否发生在其他部位以及在生理抗原加工和呈递之后是否发生尚不清楚。我们定义了单特异性 T 细胞上不同归巢表型的体内印记，这些 T 细胞响应脑内、皮下和腹膜内肿瘤表达的抗原，并在颈部淋巴结 (LN) 中交叉引发的 CD8 T 细胞具有高效的脑向性。当肿瘤存在于多个部位时，多个印记程序可以在同一淋巴结中同时发生。因此，LN 的身份在确定归巢表型方面并不是最重要的。这一关键的功能参数由交叉提呈 APC 的抗原捕获位点上游决定。
Expression of tissue-specific homing molecules directs antigen-experienced T cells to particular peripheral tissues. In studies using soluble antigens that focused on skin and gut, antigen-presenting cells (APCs) within regional lymphoid tissues were proposed to be responsible for imprinting homing phenotypes. Whether this occurs in other sites and after physiologic antigen processing and presentation is unknown. We define in vivo imprinting of distinct homing phenotypes on monospecific T cells responding to antigens expressed by tumors in intracerebral, subcutaneous, and intraperitoneal sites with efficient brain-tropism of CD8 T cells crossprimed in the cervical lymph nodes (LNs). Multiple imprinting programs could occur simultaneously in the same LN when tumors were present in more than one site. Thus, the identity of the LN is not paramount in determining the homing phenotype; this critical functional parameter is dictated upstream at the site of antigen capture by crosspresenting APCs.