Lyman W D, Brosnan C F, Kadish A S, Raine C S
Cell Immunol. 1984 May;85(2):542-8. doi: 10.1016/0008-8749(84)90266-1.
Resistance to experimental autoimmune encephalomyelitis (EAE) in Hartley guinea pigs has previously been reported to be associated with disease-specific antigen-induced suppression of mitogen responses in vitro. The present studies were initiated to investigate the requirement for different cell populations in this suppression. Intact and adherent-cell-depleted cultures of spleen cells from experimental and control animals were incubated with myelin basic protein (MBP), the major antigen of EAE, with the T-cell mitogen concanavalin A (Con A) alone or with Con A in the presence of MBP. In agreement with previous studies, MBP-induced suppression of the Con A response was observed only in cultures derived from resistant animals. In addition, it was observed that this suppression was abrogated by depletion of adherent cells. When cells from resistant and susceptible animals were mixed, suppression occurred only in the presence of nonadherent cells from resistant guinea pigs. Adherent cells from either resistant or susceptible animals functioned equally well. Cultures of purified E-rosette-forming cells (E+) from resistant animals (i.e., T cells) showed no suppression. Similarly, cells from these same animals which were depleted of E+ cells (i.e., non-T cells) did not demonstrate suppression in vitro. Upon reconstitution of spleen cell populations from resistant guinea pigs by mixing E+ and E- cells, suppression was restored. These experiments show that this model of suppression in vitro requires adherent cells as well as T cells and suggests that antigen-induced suppression of mitogen responses is dependent upon a cell-mediated immunologic mechanism.
先前有报道称,Hartley豚鼠对实验性自身免疫性脑脊髓炎(EAE)的抵抗力与疾病特异性抗原在体外诱导的丝裂原反应抑制有关。开展本研究是为了探究这种抑制中不同细胞群体的需求。将来自实验动物和对照动物的脾细胞完整培养物及去除贴壁细胞的培养物与EAE的主要抗原髓鞘碱性蛋白(MBP)、单独的T细胞丝裂原刀豆球蛋白A(Con A)或在MBP存在下与Con A一起孵育。与先前的研究一致,仅在来自抗性动物的培养物中观察到MBP诱导的Con A反应抑制。此外,还观察到去除贴壁细胞可消除这种抑制。当将来自抗性和易感动物的细胞混合时,仅在存在来自抗性豚鼠的非贴壁细胞时才会发生抑制。来自抗性或易感动物的贴壁细胞功能相同。来自抗性动物的纯化E玫瑰花结形成细胞(E+)(即T细胞)培养物未显示出抑制作用。同样,来自这些相同动物的去除E+细胞(即非T细胞)的细胞在体外也未表现出抑制作用。通过混合E+和E-细胞重建抗性豚鼠的脾细胞群体后,抑制作用得以恢复。这些实验表明,这种体外抑制模型需要贴壁细胞和T细胞,并表明抗原诱导的丝裂原反应抑制依赖于细胞介导的免疫机制。