Zang Y C, Hong J, Tejada-Simon M V, Li S, Rivera V M, Killian J M, Zhang J Z
Multiple Sclerosis Research Laboratory, Department of Neurology, Baylor College of Medicine, Houston 77030, USA.
Eur J Immunol. 2000 Mar;30(3):908-13. doi: 10.1002/1521-4141(200003)30:3<908::AID-IMMU908>3.0.CO;2-1.
T cell responses to myelin basic protein (MBP) are potentially involved in the pathogenesis of multiple sclerosis (MS). In this study, we demonstrated that subcutaneous inoculations with irradiated autologous MBP-reactive T cell clones (T cell vaccination) elicited CD8+ anti-idiotypic T cell responses and CD4+ Th2 cell responses in patients with MS. Both regulatory cell types induced by T cell vaccination contributed to the inhibition of MBP-reactive T cells while they differed in the recognition pattern and functional properties. We describe for the first time that the Th2 regulatory cells reacted with activated but not resting T cells in the context of MHC class II molecules and inhibited the proliferation of MBP-reactive T cells through the secretion of IL-4 and IL-10. The T-T cell interaction mediated by Th2 regulatory cells was independent of the antigen specificity of activated T cells. The findings have important implications for our understanding of the regulatory mechanism induced by T cell vaccination.
T细胞对髓鞘碱性蛋白(MBP)的反应可能参与了多发性硬化症(MS)的发病机制。在本研究中,我们证明,对MS患者进行皮下接种经辐照的自体MBP反应性T细胞克隆(T细胞疫苗接种)可引发CD8 +抗独特型T细胞反应和CD4 + Th2细胞反应。T细胞疫苗接种诱导的两种调节性细胞类型均有助于抑制MBP反应性T细胞,不过它们在识别模式和功能特性上有所不同。我们首次描述,Th2调节性细胞在MHC II类分子的背景下与活化而非静止的T细胞发生反应,并通过分泌IL-4和IL-10抑制MBP反应性T细胞的增殖。Th2调节性细胞介导的T-T细胞相互作用独立于活化T细胞的抗原特异性。这些发现对于我们理解T细胞疫苗接种诱导的调节机制具有重要意义。