Área Inmunología, Departamento de Biociencias (Facultad de Química) and Cátedra de Inmunología, Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay.
Área Inmunología, Departamento de Biociencias (Facultad de Química) and Cátedra de Inmunología, Instituto de Química Biológica (Facultad de Ciencias), Universidad de la República, Montevideo, Uruguay.
Semin Immunol. 2021 Mar;53:101528. doi: 10.1016/j.smim.2021.101528. Epub 2021 Nov 19.
The interaction between CD40 and CD154 (CD40 ligand) is central in immunology, participating in CD4 T cell priming by dendritic cells (DC), CD4 T cell help to B cells and classical macrophage activation by CD4 T cells. However, its role in the Th2 side of immunology including helminth infection remains incompletely understood. Contrary to viral and bacterial stimuli, helminth products usually do not cause CD40 up-regulation in DC, and exogenous CD40 ligation drives Th2-biased systems towards Th1. On the other hand, CD40 and CD154 are necessary for induction of most Th2 responses. We attempt to reconcile these observations, mainly by proposing that (i) CD40 up-regulation in DC in Th2 systems is mostly induced by alarmins, (ii) the Th2 to Th1 shift induced by exogenous CD40 ligation is related to the capacity of such ligation to enhance IL-12 production by myeloid cells, and (iii) signals elicited by endogenous CD154 available in Th2 contexts and by exogenous CD40 ligation are probably different. We stress that CD40-CD154 is important beyond cognate cellular interactions. In such a context, we argue that the proliferation response of B-cells to IL-4 plus CD154 reflects a Th2-specific mechanism for polyclonal B-cell amplification and IgE production at infection sites. Finally, we argue that CD154 is a general immune activation signal across immune polarization including Th2, and propose that competition for CD154 at tissue sites may provide negative feedback on response induction at each site.
CD40 与 CD154（CD40 配体）的相互作用在免疫学中至关重要，参与树突状细胞（DC）对 CD4 T 细胞的初始激活、CD4 T 细胞对 B 细胞的辅助作用以及 CD4 T 细胞对经典巨噬细胞的激活。然而，其在包括寄生虫感染在内的 Th2 免疫方面的作用仍不完全清楚。与病毒和细菌刺激物相反，寄生虫产物通常不会导致 DC 中 CD40 的上调，而外源性 CD40 配体则会促使 Th2 偏向系统向 Th1 转变。另一方面，CD40 和 CD154 是诱导大多数 Th2 反应所必需的。我们试图调和这些观察结果，主要是通过提出以下观点：（i）Th2 系统中 DC 中 CD40 的上调主要是由警报素诱导的；（ii）外源性 CD40 配体诱导的 Th2 向 Th1 转变与这种配体增强髓样细胞产生 IL-12 的能力有关；（iii）内源性 CD154 在 Th2 环境中以及外源性 CD40 配体诱导的信号可能不同。我们强调 CD40-CD154 的重要性不仅限于同源细胞相互作用。在这种情况下，我们认为 B 细胞对 IL-4 加 CD154 的增殖反应反映了 Th2 特异性机制，可在感染部位实现多克隆 B 细胞扩增和 IgE 产生。最后，我们认为 CD154 是免疫极化（包括 Th2）的一般性免疫激活信号，并提出组织部位对 CD154 的竞争可能会对每个部位的反应诱导产生负反馈。
