Cautain B, Damoiseaux J, Bernard I, van Straaten H, van Breda Vriesman P, Boneu B, Druet P, Saoudi A
INSERM U28, Institut Fédératif de recherche 30, and Université Paul Sabatier, Toulouse, France.
Eur J Immunol. 2001 Apr;31(4):1132-40.
Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease induced in susceptible rat strains by a single immunization with myelin basic protein (MBP). The Lewis (LEW) strain is susceptible to disease induction while the Brown Norway (BN) strain is resistant. This resistance involves non-MHC genes since congenic BN-1L rats, with LEW MHC on a BN-derived background, are also resistant. In the present study we show that, upon immunization with MBP, the non-MHC-encoded resistance to develop clinical EAE in BN-1L rats is associated with a decreased production of IFN-gamma. This may be due to a difference between LEW and BN-1L rats in their ability to produce regulatory cytokines such as IL-4, IL-10 and TGF-beta. In comparison to LEW rats, immune lymph node cells from BN-1L rats express an increased amount of IL-4 mRNA but produce less IL-10. Furthermore, the sera from BN-1L rats contain higher amounts of active TGF-beta1. Therefore, we have investigated the involvement of IL-4 and TGF-beta in the resistance of BN-1L rats to develop EAE using neutralizing mAb. Neutralization of TGF-beta, but not IL-4, renders BN-1L rats susceptible to clinical EAE without affecting the proliferation or the cytokine repertoire of immune lymph node cells. With respect to the origin of the endogenous TGF-beta production, we excluded the involvement of CD8 T cells and discuss a possible role of platelets and of CD4 T cells exhibiting the CD45RC(low) phenotype.
实验性变应性脑脊髓炎（EAE）是一种由髓鞘碱性蛋白（MBP）单次免疫诱导易感大鼠品系产生的T细胞介导的自身免疫性疾病。Lewis（LEW）品系易患该病，而棕色挪威（BN）品系具有抗性。这种抗性涉及非MHC基因，因为具有LEW MHC基因且背景为BN来源的同源BN-1L大鼠也具有抗性。在本研究中，我们发现，用MBP免疫后，BN-1L大鼠中由非MHC编码的对临床EAE发展的抗性与IFN-γ产生减少有关。这可能是由于LEW和BN-1L大鼠在产生调节性细胞因子如IL-4、IL-10和TGF-β的能力上存在差异。与LEW大鼠相比，BN-1L大鼠的免疫淋巴结细胞表达的IL-4 mRNA量增加，但产生的IL-10较少。此外，BN-1L大鼠的血清中含有更高量的活性TGF-β1。因此，我们使用中和单克隆抗体研究了IL-4和TGF-β在BN-1L大鼠对EAE发展的抗性中的作用。中和TGF-β而非IL-4使BN-1L大鼠易患临床EAE，而不影响免疫淋巴结细胞的增殖或细胞因子谱。关于内源性TGF-β产生的来源，我们排除了CD8 T细胞的参与，并讨论了血小板和表现出CD45RC（低）表型的CD4 T细胞的可能作用。
