Jiang Shuguang, Arendt Anatol, Hargrave Paul A, Adamus Grazyna
Neurological Sciences Institute, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
Cell Immunol. 2002 May-Jun;217(1-2):87-94. doi: 10.1016/s0008-8749(02)00514-2.
Lewis rats immunized with myelin basic protein (MBP) developed experimental autoimmune encephalomyelitis (EAE) and associated anterior uveitis (AU). Although several cryptic epitopes of MBP have strong encephalitogenic and uveitogenic properties, the peptide corresponding to the MBP residues 1-20 was uniquely capable of inducing AU without EAE. In this study, we showed that acetylation of the N-terminal amino acid did not produce encephalitogenicity, did not enhance uveitogenicity, and did not improve T cell proliferation in Lewis rats. The cytokine production profile induced by MBP(1-20) immunization was consistent with a Th1 response. In MBP-injected rats and in peptide-injected rats, the frequency of the IFN-gamma-secreting cells in MBP(69-89)-stimulated T cells was significantly higher than the frequency of IFN-gamma-secreting cells in MBP(1-20)-stimulated T cells. However, similar numbers of IFN-gamma-producing specific cells were found in the eyes of MBP(69-89) and MBP(1-20) immunized rats. In these rats, the iris-infiltrating cells consisted of a much higher percentage of CD4(+) T cells expressing L-selectin (CD62L) than did those cells found in the spinal cord. The results demonstrate that MBP(1-20) is immunogenic and uveitogenic, although it induced only weak proliferation and weak Th1 reaction. The fact that T cells with the same specificity have different effects on target organs suggested that, in the eye and spinal cord, a distinct mechanism might mediate the recruitment of cells to these organs.
用髓鞘碱性蛋白（MBP）免疫的Lewis大鼠发生了实验性自身免疫性脑脊髓炎（EAE）及相关的前葡萄膜炎（AU）。尽管MBP的几个隐蔽表位具有很强的致脑脊髓炎和致葡萄膜炎特性，但对应于MBP第1 - 20位残基的肽却唯独能够诱导AU而不引发EAE。在本研究中，我们发现N端氨基酸的乙酰化不会产生致脑脊髓炎作用，不会增强致葡萄膜炎作用，也不会促进Lewis大鼠的T细胞增殖。MBP(1 - 20)免疫诱导的细胞因子产生谱与Th1反应一致。在注射MBP的大鼠和注射肽的大鼠中，MBP(69 - 89)刺激的T细胞中分泌IFN-γ的细胞频率显著高于MBP(1 - 20)刺激的T细胞中分泌IFN-γ的细胞频率。然而，在MBP(69 - 89)和MBP(1 - 20)免疫的大鼠眼中发现的分泌IFN-γ的特异性细胞数量相似。在这些大鼠中，虹膜浸润细胞中表达L-选择素（CD62L）的CD4(+) T细胞百分比远高于脊髓中的浸润细胞。结果表明MBP(1 - 20)具有免疫原性和致葡萄膜炎性，尽管它仅诱导了较弱的增殖和较弱的Th1反应。具有相同特异性的T细胞对靶器官有不同作用这一事实表明，在眼睛和脊髓中，可能存在不同的机制介导细胞向这些器官的募集。
