Gautam A M, Glynn P
Multiple Sclerosis Society Laboratory, Institute of Neurology, London, UK.
J Immunol. 1990 Feb 15;144(4):1177-80.
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory neurological disease initiated by activated T cells specific for the autoantigen, myelin basic protein (MBP). The ability of Lewis rat splenic T cells to transfer EAE after in vitro incubation with MBP-pulsed dendritic cells (DC) was used as an index of MBP-specific T cell activation. OVA, previously processed by macrophages, was incubated with MBP and DC at the pulsing stage to determine whether it could inhibit presentation of the autoantigen. At molar equivalents of 2.5:1 and 20:1 relative to MBP, processed OVA increasingly inhibited the ability of DC to activate MBP-specific T cells for EAE transfer. Unprocessed OVA, which cannot be presented immunogenically by Lewis rat DC, was much less effective. However, processed OVA added to DC after they had been pulsed with MBP could not compete. OVA also blocked appearance of EAE when mixed with MBP/CFA in the inoculum used for active induction of the disease. Splenic T cells from MBP + OVA/CFA-immunized rats transferred EAE with a substantially delayed onset, suggesting that a reduced number of MBP-specific T cells was generated by immunizing with the OVA + MBP mixture compared with MBP alone. Overall, the data indicate that fragments of a foreign protein, OVA, which can be bound by APC, can also inhibit presentation of encephalitogenic determinants of MBP to T cells.
实验性自身免疫性脑脊髓炎(EAE)是一种由针对自身抗原髓鞘碱性蛋白(MBP)的活化T细胞引发的炎性神经疾病。将Lewis大鼠脾T细胞与MBP脉冲树突状细胞(DC)体外孵育后转移EAE的能力用作MBP特异性T细胞活化的指标。在脉冲阶段,将先前由巨噬细胞处理过的卵清蛋白(OVA)与MBP和DC一起孵育,以确定其是否能抑制自身抗原的呈递。相对于MBP,当摩尔当量为2.5:1和20:1时,处理过的OVA越来越能抑制DC激活MBP特异性T细胞进行EAE转移的能力。未经处理的OVA不能被Lewis大鼠DC免疫原性呈递,其效果要差得多。然而,在DC用MBP脉冲后加入处理过的OVA则无法竞争。当OVA与用于主动诱导该疾病的接种物中的MBP/CFA混合时,OVA也能阻止EAE的出现。来自MBP + OVA/CFA免疫大鼠的脾T细胞转移EAE时发病明显延迟,这表明与单独用MBP免疫相比,用OVA + MBP混合物免疫产生的MBP特异性T细胞数量减少。总体而言,数据表明可被抗原呈递细胞(APC)结合的外来蛋白质OVA片段也能抑制MBP致脑炎决定簇向T细胞的呈递。