Young Neil T, Waller Edward C P, Patel Rashmi, Roghanian Ali, Austyn Jonathan M, Trowsdale John
Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, UK.
Blood. 2008 Mar 15;111(6):3090-6. doi: 10.1182/blood-2007-05-089771. Epub 2007 Dec 19.
Dendritic cells (DCs) link innate and adaptive immunity, initiating and regulating effector cell responses. They ubiquitously express members of the LILR (ILT, LIR, CD85) family of molecules, some of which recognize self-HLA molecules, but little is known of their possible functions in DC biology. We demonstrate that the inhibitory receptor LILRB1 (ILT2, LIR1, CD85j) is selectively up-regulated during DC differentiation from monocyte precursors in culture. Continuous ligation of LILRB1 modulated cellular differentiation, conferred a unique phenotype upon the resultant cells, induced a profound resistance to CD95-mediated cell death, and inhibited secretion of cytokines IL-10, IL-12p70, and TGF-beta. These features remained stable even after exposure of the cells to bacterial LPS. Ligated DCs exhibited poor stimulatory activity for primary and memory T-cell proliferative responses, but this was substantially reversed by blockade of CD80 or its preferred ligand CTLA-4, or by depleting CD4(+) CD25(+) CD127(lo) regulatory T cells. Our findings suggest that ligation of LILRB1 on DCs by self-HLA molecules may play a key role in controlling the balance between the induction and suppression of adaptive immune responses.
树突状细胞（DCs）连接先天性免疫和适应性免疫，启动并调节效应细胞反应。它们普遍表达LILR（ILT、LIR、CD85）分子家族的成员，其中一些成员可识别自身HLA分子，但对其在DC生物学中的潜在功能知之甚少。我们证明，抑制性受体LILRB1（ILT2、LIR1、CD85j）在培养的单核细胞前体向DC分化过程中被选择性上调。LILRB1的持续连接调节细胞分化，赋予所得细胞独特的表型，诱导对CD95介导的细胞死亡产生深刻抗性，并抑制细胞因子IL-10、IL-12p70和TGF-β的分泌。即使在细胞暴露于细菌脂多糖后，这些特征仍保持稳定。被连接的DC对初始和记忆性T细胞增殖反应的刺激活性较差，但通过阻断CD80或其首选配体CTLA-4，或通过消耗CD4(+) CD25(+) CD127(lo)调节性T细胞，这种情况可得到显著逆转。我们的研究结果表明，自身HLA分子对DC上LILRB1的连接可能在控制适应性免疫反应的诱导和抑制之间的平衡中起关键作用。
