Yang T H, Aosai F, Norose K, Ueda M, Yano A
Department of Medical Zoology, Nagasaki University School of Medicine, Japan.
J Immunol. 1995 Jan 1;154(1):290-8.
CD4+ lines specific for Toxoplasma gondii-infected human melanoma P36 cells were established from PBL of a patient with chronic toxoplasmosis. CD4+ CTL lines were obtained by weekly in vitro stimulation with T. gondii-infected P36 cells that shared HLA-DR4 molecules with the patient. The lytic activity of CD4+ CTL lines against T. gondii-infected P36 or T. gondii-infected autologous EBV-transformed B lymphoma (EBV-Ya) was inhibited by anti-HLA-DR mAb, whereas anti-HLA-A, B, C mAb failed to block the lytic activity. Thus, the cytotoxicity of CD4+ CTL lines against T. gondii-infected P36 was restricted by HLA-DR molecules. In response to Ag-specific stimulation, CD4+ CTL lines produced significant levels of IFN-gamma. Exogenously added IFN-gamma up-regulated the surface expression of MHC class II, but not of class I in T. gondii-infected P36 cells. In addition, the CTL activity against T. gondii-infected P36 cells was augmented when target cells were co-cultured with IFN-gamma. These data indicate that CD4+ CTL-mediated cytotoxicity against T. gondii-infected melanocytes is enhanced by the autocrine production of IFN-gamma. Further, CD4+ CTL may play a role in the manifestation of toxoplasmic retinochoroiditis by killing T. gondii-infected melanocytes.
从一名慢性弓形虫病患者的外周血淋巴细胞（PBL）中建立了针对弓形虫感染的人黑色素瘤P36细胞的CD4 +细胞系。通过每周用与患者共享HLA - DR4分子的弓形虫感染的P36细胞进行体外刺激获得CD4 +细胞毒性T淋巴细胞（CTL）系。抗HLA - DR单克隆抗体抑制了CD4 + CTL系对弓形虫感染的P36或弓形虫感染的自体EB病毒转化的B淋巴瘤（EBV - Ya）的裂解活性，而抗HLA - A、B、C单克隆抗体未能阻断裂解活性。因此，CD4 + CTL系对弓形虫感染的P36的细胞毒性受HLA - DR分子限制。响应抗原特异性刺激，CD4 + CTL系产生了显著水平的γ干扰素（IFN - γ）。外源添加的IFN - γ上调了弓形虫感染的P36细胞中MHC II类分子的表面表达，但未上调I类分子的表面表达。此外，当靶细胞与IFN - γ共培养时，对弓形虫感染的P36细胞的CTL活性增强。这些数据表明，IFN - γ的自分泌产生增强了CD4 + CTL介导的对弓形虫感染的黑色素细胞的细胞毒性。此外，CD4 + CTL可能通过杀死弓形虫感染的黑色素细胞在弓形虫性视网膜脉络膜炎的表现中发挥作用。
