McDonald A H, Swanborg R H
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201.
J Immunol. 1988 Feb 15;140(4):1132-8.
Previous work from this laboratory has revealed that spleen and/or lymph node cells from Lewis rats, that have recovered from an acute episode of experimental autoimmune encephalomyelitis (EAE), suppress the development of EAE when injected into syngeneic recipients subsequently challenged with myelin basic protein (MBP) in CFA. In an effort to understand the mechanism of this suppression, we measured the production of immune IFN-gamma, which may be required for the induction of an immune response, by EAE effector T cells (which transfer disease) and EAE suppressor cells when cultured in vitro with MBP. We now report that EAE effector T cells produce IFN-gamma when cultured in vitro with MBP. In contrast, spleen cells from recovered rats (which manifest suppressor activity in vivo) do not produce IFN-gamma. Moreover, in cell mixing experiments, these suppressor spleen cells inhibited the production of IFN-gamma by EAE effector cells. This inhibition was not eliminated by the removal of macrophages nor by the inhibition of PG synthesis by indomethacin. Furthermore, the inhibition was shown to be Ag-specific and mediated by nylon-adherent, radiation-sensitive splenic T cells. The findings suggest that suppressor cells regulate EAE by inhibiting IFN-gamma production by effector cells. This inhibition may result in the down-regulation of IFN-gamma-induced expression of class II major histocompatibility Ag on cells of the central nervous system, thus reducing the presentation of tissue-specific Ag (i.e., MBP) to autoreactive lymphocytes.
该实验室之前的研究表明，从实验性自身免疫性脑脊髓炎（EAE）急性发作中恢复的Lewis大鼠的脾脏和/或淋巴结细胞，当注入同基因受体并随后用CFA中的髓鞘碱性蛋白（MBP）攻击时，可抑制EAE的发展。为了理解这种抑制的机制，我们测量了EAE效应T细胞（传递疾病）和EAE抑制细胞在体外与MBP一起培养时免疫干扰素-γ的产生，免疫干扰素-γ可能是诱导免疫反应所必需的。我们现在报告，EAE效应T细胞在体外与MBP一起培养时产生干扰素-γ。相比之下，恢复大鼠的脾细胞（在体内表现出抑制活性）不产生干扰素-γ。此外，在细胞混合实验中，这些抑制性脾细胞抑制了EAE效应细胞产生干扰素-γ。去除巨噬细胞或用消炎痛抑制PG合成并不能消除这种抑制。此外，这种抑制被证明是抗原特异性的，并且由尼龙粘附、辐射敏感的脾T细胞介导。这些发现表明，抑制细胞通过抑制效应细胞产生干扰素-γ来调节EAE。这种抑制可能导致干扰素-γ诱导的中枢神经系统细胞上II类主要组织相容性抗原表达的下调，从而减少组织特异性抗原（即MBP）向自身反应性淋巴细胞的呈递。
