Issazadeh S, Mustafa M, Ljungdahl A, Höjeberg B, Dagerlind A, Elde R, Olsson T
Department of Clinical Neurosciences and Family Medicine, Huddinge University Hospital, Karolinska Institute, Sweden.
J Neurosci Res. 1995 Apr 1;40(5):579-90. doi: 10.1002/jnr.490400503.
The potential role of certain important immunoregulatory and effector cytokines in autoimmune neuroinflammation have been studied. We have examined the expression of mRNA, with in situ hybridization, of interferon gamma (IFN-gamma), interleukin 4 (IL-4) and transforming growth factor beta (TGF-beta) both in sections of spinal cords and the antigen-induced expression of these cytokines by lymphoid cells after stimulation with a dominant encephalitogenic peptide of MBP (MBP 63-88) during the course of actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats. In spinal cords, the target organ in EAE, cells expressing mRNA for IFN-gamma, first appeared at the onset of clinical signs, i.e., day 10 postimmunization (p.i.), peaked at the height of disease (day 13 p.i.) and then gradually decreased concomitant with recovery. Very few IL-4 mRNA-expressing cells appeared in the spinal cord with no clear relation to clinical signs or histopathology. In contrast, expression of mRNA for TGF-beta did not increase until day 13 p.i., at height of the disease, shortly preceding recovery. These data are consistent with a disease upregulating role of IFN-gamma, while TGF-beta may act to limit central nervous system (CNS) inflammation. In lymphoid organs, primed MBP 63-88 reactive T cells showed an interesting time-dependent evolution of their cytokine production in vitro. Thus, early after immunization there was a conspicuous MBP 63-88-induced production of both IFN-gamma and IL-4. Such cells may act in the initiation and promotion of the disease. Later, in the recovery phase, MBP 63-88 induced lymphoid cells to TGF-beta production. Thus, an autoantigen-specific production of TGF-beta occurred during EAE and hypothetically such a mechanism may serve to downregulate aggressive autoimmunity systemically.
已经研究了某些重要的免疫调节和效应细胞因子在自身免疫性神经炎症中的潜在作用。我们通过原位杂交检测了干扰素γ（IFN-γ）、白细胞介素4（IL-4）和转化生长因子β（TGF-β）在脊髓切片中的mRNA表达，以及在Lewis大鼠主动诱导实验性自身免疫性脑脊髓炎（EAE）过程中，用髓鞘碱性蛋白（MBP）的显性致脑炎性肽（MBP 63-88）刺激后，这些细胞因子由淋巴细胞进行的抗原诱导表达。在EAE的靶器官脊髓中，表达IFN-γ mRNA的细胞在临床症状出现时，即免疫后第10天首次出现，在疾病高峰期（免疫后第13天）达到峰值，然后随着恢复逐渐减少。脊髓中很少有表达IL-4 mRNA的细胞出现，与临床症状或组织病理学无明显关系。相比之下，TGF-β mRNA的表达直到免疫后第13天，即疾病高峰期、恢复前不久才增加。这些数据与IFN-γ在疾病上调中的作用一致，而TGF-β可能起到限制中枢神经系统（CNS）炎症的作用。在淋巴器官中，致敏的MBP 63-88反应性T细胞在体外显示出其细胞因子产生的有趣的时间依赖性演变。因此，免疫后早期，MBP 63-88可显著诱导IFN-γ和IL-4的产生。这类细胞可能在疾病的起始和进展中起作用。后来，在恢复阶段，MBP 63-88诱导淋巴细胞产生TGF-β。因此，在EAE期间发生了自身抗原特异性的TGF-β产生，假设这种机制可能在全身下调侵袭性自身免疫。
