Lee Koutetsu, Takenaka Hiroshi, Yoneda Yukio, Goto Toshiyuki, Sano Kouichi, Nakanishi Mahito, Eguchi Akiko, Okada Masashi, Tashiro Junko, Sakurai Kanji, Kubota Takahiro, Yoshida Ryotaro
Department of Physiology, Osaka Medical College, Takatsuki, Osaka, Japan.
Microbiol Immunol. 2004;48(1):15-25. doi: 10.1111/j.1348-0421.2004.tb03483.x.
CD8(+) cytotoxic T lymphocytes (CTLs) generated by immunization with allogeneic cells or viral infection are able to lyse allogeneic or virally infected in vitro cells (e.g., lymphoma and mastocytoma). In contrast, it is reported that CD8(+) T cells are not essential for allograft rejection (e.g., heart and skin), and that clearance of influenza or the Sendai virus from virus-infected respiratory epithelium is normal or only slightly delayed after a primary viral challenge of CD8-knockout mice. To address this controversy, we generated H-2(d)-specific CD8(+) CTLs by a mixed lymphocyte culture and examined the susceptibility of a panel of H-2(d) cells to CTL lysis. KLN205 squamous cell carcinoma, Meth A fibrosarcoma, and BALB/c skin components were found to be resistant to CTL-mediated lysis. This resistance did not appear to be related to a reduced expression of MHC class I molecules, and all these cells could block the recognition of H-2(d) targets by CTLs in cold target inhibition assays. We extended our observation by persistently infecting the same panel of cell lines with defective-interfering Sendai virus particles. The Meth A and KLN205 lines infected with a variant Sendai virus were resistant to lysis by Sendai virus-specific CTLs. The Sendai virus-infected Meth A and KLN205 lines were able to block the lysis of Sendai virus-infected targets by CTLs in cold target inhibition assays. Taken together, these results suggest that not all in vivo tissues may be sensitive to CTL lysis.
通过同种异体细胞免疫或病毒感染产生的CD8(+) 细胞毒性T淋巴细胞（CTL）能够在体外裂解同种异体或病毒感染的细胞（如淋巴瘤和肥大细胞瘤）。相比之下，有报道称CD8(+) T细胞对于同种异体移植排斥（如心脏和皮肤）并非必不可少，并且在对CD8基因敲除小鼠进行初次病毒攻击后，流感病毒或仙台病毒从病毒感染的呼吸道上皮细胞中的清除是正常的或仅略有延迟。为了解决这一争议，我们通过混合淋巴细胞培养产生了H-2(d)特异性CD8(+) CTL，并检测了一组H-2(d)细胞对CTL裂解的敏感性。发现KLN205鳞状细胞癌、Meth A纤维肉瘤和BALB/c皮肤成分对CTL介导的裂解具有抗性。这种抗性似乎与MHC I类分子表达降低无关，并且在冷靶抑制试验中，所有这些细胞都能阻断CTL对H-2(d)靶标的识别。我们通过用缺陷干扰性仙台病毒颗粒持续感染同一组细胞系来扩展我们的观察。感染了变异仙台病毒的Meth A和KLN205细胞系对仙台病毒特异性CTL的裂解具有抗性。在冷靶抑制试验中，感染仙台病毒的Meth A和KLN205细胞系能够阻断CTL对感染仙台病毒的靶标的裂解。综上所述，这些结果表明并非所有体内组织都对CTL裂解敏感。
