Fujino Y, Okumura A, Nussenblatt R B, Gery I, Mochizuki M
Department of Ophthalmology, Kanto Chuo Hospital, Tokyo, Japan.
Clin Immunol Immunopathol. 1988 Feb;46(2):234-48. doi: 10.1016/0090-1229(88)90186-9.
Cyclosporine (CsA) was previously reported to effectively suppress the induction of experimental autoimmune uveoretinitis (EAU) in rats immunized with S-antigen. The present study provides information concerning the development of specific unresponsiveness in the CsA-treated rats. The majority of Lewis rats immunized with S-antigen and treated with CsA from Day 0 to Day 14 failed to develop EAU when reimmunized with S-antigen on Day 30. In contrast, similarly treated rats were fully susceptible to induction of experimental allergic encephalomyelitis when immunized with myelin basic protein, or even to EAU when immunized with another retinal antigen, interphotoreceptor retinoid-binding protein (IRBP). The possible involvement of suppressor cells in establishing the unresponsiveness state was indicated by experiments both in vitro and in vivo. The enriched fractions of suppressor cells from rats unresponsive to induction of EAU by S-antigen were found to inhibit the specific mitotic response of lymphocytes to S-antigen, but had no effect on the response to IRBP. In vivo, injection of such enriched suppressor cell fractions to naive syngenic rats inhibited or delayed the development of EAU following immunization with S-antigen. It is proposed, therefore, that specific unresponsiveness plays a role in the suppression of EAU by CsA and that the unresponsiveness is mediated in part by specific suppressor cells.
环孢素（CsA）先前曾被报道能有效抑制用S抗原免疫的大鼠实验性自身免疫性葡萄膜视网膜炎（EAU）的诱发。本研究提供了有关经CsA处理的大鼠特异性无反应性发展情况的信息。大多数从第0天到第14天用S抗原免疫并经CsA处理的Lewis大鼠，在第30天再次用S抗原免疫时未发生EAU。相比之下，同样处理的大鼠在用髓鞘碱性蛋白免疫时对实验性变应性脑脊髓炎的诱发完全敏感，甚至在用另一种视网膜抗原，即光感受器间类视黄醇结合蛋白（IRBP）免疫时对EAU也完全敏感。体外和体内实验均表明抑制细胞可能参与了无反应性状态的建立。发现来自对S抗原诱发EAU无反应的大鼠的抑制细胞富集组分能抑制淋巴细胞对S抗原的特异性有丝分裂反应，但对其对IRBP的反应无影响。在体内，将这种富集的抑制细胞组分注射到同基因的未免疫大鼠中，可抑制或延缓用S抗原免疫后EAU的发展。因此，有人提出特异性无反应性在CsA对EAU的抑制中起作用，且这种无反应性部分是由特异性抑制细胞介导的。
