Esa A H, Converse P J, Hess A D
Johns Hopkins Bone Marrow Transplantation Program Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Int J Immunopharmacol. 1987;9(8):893-902. doi: 10.1016/0192-0561(87)90005-1.
We examined whether cyclosporine (CsA) interferes with human monocyte processing and presentation of soluble and particulate antigens. Human monocytes were pulsed in the presence of CsA with one of three antigens: tetanus toxoid (TT), diphtheria toxoid (DIP) or cytomegalovirus (CMVx). When these monocytes were co-cultured with immunocompetent T-lymphocytes they were found to be impaired in the induction of proliferative and cytotoxic T-cell responses. At CsA concentrations higher that 0.5 micrograms/ml, proliferation induced by the particulate CMVx antigen was markedly more sensitive than that induced by the soluble TT antigen. In the allogeneic mixed lymphocyte reaction (MLR), pretreatment of responder haplotype monocytes alone with CsA led to reduced reactivity as determined in both proliferative (P less than 0.01) and cell-mediated lympholysis (P less than 0.001) assays. These effects of CsA were not due to direct CsA action of residual CsA carried over with treated monocytes, and were not apparently due to inhibition of interleukin-1 (IL-1) production since exogenous IL-1 could not restore normal responses.
我们研究了环孢素(CsA)是否会干扰人单核细胞对可溶性和颗粒性抗原的处理及呈递。在存在CsA的情况下,用人单核细胞与三种抗原之一进行脉冲处理:破伤风类毒素(TT)、白喉类毒素(DIP)或巨细胞病毒(CMVx)。当这些单核细胞与具有免疫活性的T淋巴细胞共培养时,发现它们在诱导增殖性和细胞毒性T细胞反应方面受到损害。当CsA浓度高于0.5微克/毫升时,颗粒性CMVx抗原诱导的增殖比可溶性TT抗原诱导的增殖明显更敏感。在同种异体混合淋巴细胞反应(MLR)中,仅用CsA预处理反应者单倍型单核细胞会导致反应性降低,这在增殖(P<0.01)和细胞介导的淋巴细胞溶解(P<0.001)试验中均得到证实。CsA的这些作用并非由于与处理过的单核细胞一起残留的CsA的直接作用,而且显然也不是由于对白介素-1(IL-1)产生的抑制,因为外源性IL-1无法恢复正常反应。