Boehm Thomas, Scheu Stefanie, Pfeffer Klaus, Bleul Conrad C
Max Planck Institute for Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany.
J Exp Med. 2003 Sep 1;198(5):757-69. doi: 10.1084/jem.20030794.
Thymocytes depend on the interaction with thymic epithelial cells for the generation of a diverse, nonautoreactive T cell repertoire. In turn, thymic epithelial cells acquire their three-dimensional cellular organization via instructive signals from developing thymocytes. The nature of these signals has been elusive so far. We show that thymocytes and medullary epithelial cells (MECs) communicate via the lymphotoxin beta receptor (LTbetaR) signaling axis. Normal differentiation of thymic MECs requires LTbetaR ligand on thymocytes and LTbetaR together with nuclear factor-kappaB-inducing kinase (Nik) in thymic epithelial cells. Impaired lympho-epithelial cross talk in the absence of the LTbetaR causes aberrant differentiation and reduced numbers of thymic MECs, leads to the retention of mature T lymphocytes, and is associated with autoimmune phenomena, suggesting an unexpected role for LTbetaR signaling in central tolerance induction.
胸腺细胞依赖于与胸腺上皮细胞的相互作用来产生多样化的、无自身反应性的T细胞库。反过来，胸腺上皮细胞通过发育中的胸腺细胞发出的指导信号获得其三维细胞组织结构。到目前为止，这些信号的性质一直难以捉摸。我们发现胸腺细胞与髓质上皮细胞（MEC）通过淋巴毒素β受体（LTβR）信号轴进行通信。胸腺MEC的正常分化需要胸腺细胞上的LTβR配体以及胸腺上皮细胞中的LTβR和核因子κB诱导激酶（Nik）。在缺乏LTβR的情况下，淋巴上皮细胞间的串扰受损会导致胸腺MEC异常分化和数量减少，导致成熟T淋巴细胞滞留，并与自身免疫现象相关，这表明LTβR信号在中枢耐受诱导中具有意想不到的作用。
