Diehl L, Den Boer A T, van der Voort E I, Melief C J, Offringa R, Toes R E
Department of Immunohematology and Blood Transfusion, Medical Center, Leiden University, The Netherlands.
J Mol Med (Berl). 2000;78(7):363-71. doi: 10.1007/s001090000126.
CD40 and CD40 ligand (CD40L) have been implicated as important molecules for the transformation of nonactivated antigen-presenting cells (APC) into cells that are potent inducers of cytotoxic T lymphocyte (CTL) immunity. The onset of a successful immune response lies within the control of the CD4+ T helper cells which, after specific antigen recognition, can up-regulate CD40L and subsequently activate APC through CD40 signaling. Triggering of CD40 with antibodies in vivo can replace the need for CD40L-expressing CD4+ T helper cells for cross-priming of CTL. Blocking of CD40-CD40L interactions can also have profound effects on the generation of T cell immunity. Interestingly, differential involvement of CD40/CD40L in immune responses can be observed between various immunological sites in the body. In most sites of the periphery interruption of CD40-CD40L interactions can lead to the induction of T cell tolerance whereas in mucosal tissues this interruption can lead to abrogation of T cell tolerance. Furthermore, in vivo CD40 activation can convert specific T cell tolerance following peptide vaccination into efficient T cell priming. Thus intervention of CD40-CD40L interactions can result in enhancement or down-modulation of T cell reactivity and therefore modulation of these interactions may form the foundation of new treatment modalities directed against malignancies, allergies, organ rejections and autoimmunity.
CD40和CD40配体（CD40L）被认为是将未活化的抗原呈递细胞（APC）转化为细胞毒性T淋巴细胞（CTL）免疫有效诱导剂的重要分子。成功免疫反应的起始取决于CD4 + T辅助细胞的控制，这些细胞在特异性抗原识别后，可以上调CD40L并随后通过CD40信号激活APC。体内用抗体触发CD40可以替代表达CD40L的CD4 + T辅助细胞对CTL交叉启动的需求。阻断CD40 - CD40L相互作用也会对T细胞免疫的产生产生深远影响。有趣的是，在体内不同免疫部位可以观察到CD40 / CD40L在免疫反应中的不同参与情况。在外周的大多数部位，CD40 - CD40L相互作用的中断可导致T细胞耐受性的诱导，而在粘膜组织中，这种中断可导致T细胞耐受性的废除。此外，体内CD40激活可将肽疫苗接种后的特异性T细胞耐受性转化为有效的T细胞启动。因此，干预CD40 - CD40L相互作用可导致T细胞反应性的增强或下调，因此调节这些相互作用可能构成针对恶性肿瘤、过敏、器官排斥和自身免疫的新治疗模式的基础。
