Gregorian S K, Clark L, Heber-Katz E, Amento E P, Rostami A
Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia 19104.
Cell Immunol. 1993 Sep;150(2):298-310. doi: 10.1006/cimm.1993.1198.
Neuritogenic T cells specific for SP-26, a synthetic peptide (residue 53-78) of myelin P2 protein that causes experimental autoimmune neuritis (EAN), use the same T cell receptor (TCR) V gene family (V beta 8) that can induce experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Tolerance to autoregulatory T cells may be induced in rats by intravenous (iv) administration of antigen-coupled splenocytes; however, the mechanisms that lead to altered immune reactivity are not well understood. Here we demonstrate that SP-26, when coupled to syngeneic spleen cells and administered iv, either before or after disease induction, markedly inhibited development and expression of clinical signs and histological changes of EAN. The induction of tolerance by this method was peptide-specific and MHC-restricted. We showed previously that T cells involved in EAN utilize the T cell antigen receptor V beta 8, whereas less than 5% of normal rat peripheral T cells express V beta 8. We have examined T lymphocytes from tolerized rats to determine the presence or absence of V beta 8(+)-bearing cells in order to determine the mechanism of tolerance. V beta 8 cells were undetectable by Northern blot analysis in the lymph nodes of unimmunized animals but easily detected in SP-26-primed and tolerized rats. In addition, spleen cells isolated from tolerized animals were anergic and failed to proliferate in response to SP-26, but retained responsiveness to IL-2 and Con A stimulation. Thus, the peptide-specific unresponsiveness that can be induced in rats with EAN, a T-cell-mediated process that is MHC-restricted and utilizes the T cell receptor V beta 8, occurs while V beta 8 transcripts remain readily detectable in spleen and lymph node cells. The detection of V beta 8-bearing T cells requires the development of antibodies specific for this rat surface protein.
髓鞘P2蛋白的合成肽（残基53 - 78）SP - 26可引发实验性自身免疫性神经炎（EAN），针对SP - 26的致神经炎性T细胞与可在Lewis大鼠中诱导实验性自身免疫性脑脊髓炎（EAE）的T细胞受体（TCR）V基因家族（Vβ8）相同。静脉注射（iv）抗原偶联的脾细胞可在大鼠中诱导对自身调节性T细胞的耐受性；然而，导致免疫反应性改变的机制尚不清楚。在此我们证明，SP - 26与同基因脾细胞偶联并静脉注射，在疾病诱导之前或之后，均能显著抑制EAN临床症状的发展和表达以及组织学变化。通过这种方法诱导的耐受性具有肽特异性且受MHC限制。我们之前表明，参与EAN的T细胞利用T细胞抗原受体Vβ8，而正常大鼠外周T细胞中表达Vβ8的比例不到5%。我们检查了耐受大鼠的T淋巴细胞，以确定是否存在携带Vβ8的细胞，从而确定耐受机制。通过Northern印迹分析，在未免疫动物的淋巴结中未检测到Vβ8细胞，但在经SP - 26致敏和耐受的大鼠中很容易检测到。此外，从耐受动物分离的脾细胞无反应性，对SP - 26刺激不增殖，但对IL - 2和刀豆蛋白A刺激仍保持反应性。因此，在EAN大鼠中可诱导的肽特异性无反应性，这是一个受MHC限制且利用T细胞受体Vβ8的T细胞介导过程，发生在脾和淋巴结细胞中Vβ8转录本仍易于检测到的时候。检测携带Vβ8的T细胞需要开发针对这种大鼠表面蛋白的特异性抗体。
