Nembrini Chiara, Reissmann Regina, Kopf Manfred, Marsland Benjamin J
Institute of Integrative Biology, Molecular Biomedicine, ETH Zürich, Swiss Federal Institute of Technology, Wagistrasse 27, CH-8952 Zurich-Schlieren, Switzerland.
Microbes Infect. 2008 Apr;10(5):522-30. doi: 10.1016/j.micinf.2008.01.016. Epub 2008 Feb 8.
The serine/threonine kinase RIP2 has been reported to be essential for Nod1 and Nod2 mediated cell activation, and has been suggested to play a role in the signaling cascade downstream of the T-cell receptor. We sought to ascertain the exact role of RIP2 in T-helper cell differentiation and CD8+ T-cell effector function in vivo and in vitro. In contrast to previous reports, we found that RIP2-deficient T cells did not exhibit impaired proliferation upon TCR engagement in vitro, and differentiation to cytokine producing Th1 or Th2 cells was normal in the absence of RIP2. These results were confirmed in vivo, as wild-type and RIP2-deficient virus-specific CD8+ T cells expanded comparably in mice after LCMV infection. Wild-type and RIP2-deficient CD4+ and CD8+ T cells from infected mice also showed similar proliferation and cytokine production when restimulated with full or partial agonist peptides ex vivo. Furthermore, no significant difference in adaptive T-cell responses could be observed between wild-type and RIP2-deficient mice after Listeria monocytogenes infection. Thus contrary to early reports, our data show that RIP2 is not an essential component of the TCR signaling machinery.
据报道，丝氨酸/苏氨酸激酶RIP2对于Nod1和Nod2介导的细胞激活至关重要，并且有人认为它在T细胞受体下游的信号级联反应中发挥作用。我们试图确定RIP2在体内和体外T辅助细胞分化及CD8 + T细胞效应功能中的确切作用。与之前的报道相反，我们发现RIP2缺陷型T细胞在体外TCR激活后并未表现出增殖受损，并且在缺乏RIP2的情况下向产生细胞因子的Th1或Th2细胞的分化是正常的。这些结果在体内得到了证实，因为野生型和RIP2缺陷型病毒特异性CD8 + T细胞在LCMV感染后的小鼠中扩增情况相当。当用完全或部分激动剂肽在体外再次刺激时，来自感染小鼠的野生型和RIP2缺陷型CD4 +和CD8 + T细胞也表现出相似的增殖和细胞因子产生。此外，在单核细胞增生李斯特菌感染后，野生型和RIP2缺陷型小鼠之间未观察到适应性T细胞反应的显著差异。因此，与早期报道相反，我们的数据表明RIP2不是TCR信号传导机制的必需组成部分。
