Neuroimmunology Research R&D-31, Portland VA Medical Center, Portland, OR 97239, USA.
J Neuroimmunol. 2010 Aug 25;225(1-2):52-61. doi: 10.1016/j.jneuroim.2010.04.013. Epub 2010 May 23.
Recombinant T cell ligands (RTLs) ameliorate experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner. We evaluated effects of RTL401 (I-A(s) alpha1beta1+PLP-139-151) on splenocytes from SJL/J mice with EAE to study RTL-T cell tolerance-inducing mechanisms. RTLs bound to B, macrophages and DCs, through RTL-MHC-alpha1beta1 moiety. RTL binding reduced CD11b expression on splenic macrophages/DC, and RTL401-conditioned macrophages/DC, not B cells, inhibited T cell activation. Reduced ability of RTL- incubated splenocytes to transfer EAE was likely mediated through macrophages/DC, since B cells were unnecessary for RTL treatment of EAE. These results demonstrate a novel pathway of T cell regulation by RTL-bound APCs.
重组 T 细胞配体(RTLs)以抗原特异性方式改善实验性自身免疫性脑脊髓炎(EAE)。我们评估了 RTL401(I-A(s)alpha1beta1+PLP-139-151)对 SJL/J 小鼠 EAE 脾细胞的影响,以研究 RTL-T 细胞耐受诱导机制。RTLs 通过 RTL-MHC-alpha1beta1 部分与 B 细胞、巨噬细胞和 DC 结合。RTL 结合降低了脾脏巨噬细胞/DC 上的 CD11b 表达,而 RTL401 调理的巨噬细胞/DC(而非 B 细胞)抑制 T 细胞激活。RTL 孵育的脾细胞传递 EAE 的能力降低可能是通过巨噬细胞/DC 介导的,因为 B 细胞对于 RTL 治疗 EAE 是不必要的。这些结果表明了 RTL 结合 APC 调节 T 细胞的新途径。