Faunce Douglas E, Terajewicz Ania, Stein-Streilein Joan
Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.
J Immunol. 2004 Feb 15;172(4):1991-5. doi: 10.4049/jimmunol.172.4.1991.
APC exposed to TGFbeta2 and Ag (tolerogenic APC) promote peripheral Ag-specific tolerance via the induction of CD8(+) T regulatory cells capable of suppressing Th1 and Th2 immunity. We postulated that tolerogenic APC might reinstate tolerance toward self-neuronal Ags and ameliorate ongoing experimental autoimmune encephalomyelitis (EAE). Seven days after immunization with myelin basic protein (MBP), mice received MBP-specific tolerogenic APC, and EAE was evaluated clinically. To test for the presence and the phenotype of T regulatory cells, CD4 and/or CD8 T cells from tolerogenic APC-treated mice were transferred to naive mice before their immunization with MBP. The MBP-specific tolerogenic APC decreased both the severity and incidence of ongoing EAE. Tolerance to self-neuronal Ags was induced in naive recipient mice via adoptive transfer of CD8(+), but not CD4(+) T cells. Rational use of in vitro-generated tolerogenic APC may lead to novel therapy for autoimmune disease.
暴露于转化生长因子β2和抗原（耐受性抗原呈递细胞）的抗原呈递细胞（APC）通过诱导能够抑制Th1和Th2免疫的CD8(+)调节性T细胞促进外周抗原特异性耐受。我们推测，耐受性APC可能恢复对自身神经元抗原的耐受性，并改善正在进行的实验性自身免疫性脑脊髓炎（EAE）。在用髓鞘碱性蛋白（MBP）免疫7天后，小鼠接受MBP特异性耐受性APC，并对EAE进行临床评估。为了检测调节性T细胞的存在和表型，将来自耐受性APC处理小鼠的CD4和/或CD8 T细胞在其用MBP免疫之前转移到未免疫的小鼠中。MBP特异性耐受性APC降低了正在进行的EAE的严重程度和发病率。通过CD8(+)而非CD4(+) T细胞的过继转移，在未免疫的受体小鼠中诱导了对自身神经元抗原的耐受性。合理使用体外产生的耐受性APC可能会带来自身免疫性疾病的新疗法。
