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对前房内同种异体肿瘤的细胞毒性T细胞反应分析

Analysis of cytotoxic T cell responses to intracameral allogeneic tumors.

作者信息

Ksander B R, Streilein J W

机构信息

Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.

出版信息

Invest Ophthalmol Vis Sci. 1989 Feb;30(2):323-9.

PMID:2492486
Abstract

Injection of P815 mastocytoma tumor cells into the anterior chamber (AC) of BALB/c mice results in progressively growing intraocular tumors, whereas injection of the same dose of tumor cells subcutaneously results in rapid rejection of the tumor. Previous results indicated that AC P815 inoculation results in an unorthodox immune response characterized by suppressed delayed hypersensitivity, elevated antibody levels and priming for cytotoxic T lymphocyte (CTL) activity. Since mice inoculated in the AC with P815 cells display progressively growing intraocular tumors in spite of the fact they are primed for CTL activity, we examined whether the differential tumor growth patterns between AC and SC inoculation are the result of an aberrant and weak cytotoxic response in the former. We analyzed the lytic activity, target specificity and frequency of cytotoxic precursors and effector cells in the spleen following AC and SC inoculation of P815 cells. Our results indicate that both AC and SC routes of P815 inoculation generate splenic CTL effector cells with equivalent lytic activity for P815 tumor target cells. These effectors are highly specific for P815 cells and do not lyse third-party EL-4 targets. Analysis of the frequency of cytotoxic T cell precursors (pTc) in the spleen and lymph nodes of animals that received AC and SC injections revealed that both routes generated comparable pTc frequencies. Thus, tumor cells placed in the anterior chamber are capable of generating a full complement of cytotoxic precursors and effectors, that are equivalent to those that are generated following SC injection. Therefore, the progressive growth of the tumor in the eye cannot be attributed to a defect in the tumor-specific CTL response.

摘要

将P815肥大细胞瘤细胞注射到BALB/c小鼠的前房(AC)中会导致眼内肿瘤逐渐生长,而皮下注射相同剂量的肿瘤细胞则会导致肿瘤迅速被排斥。先前的结果表明,前房接种P815会引发一种非传统的免疫反应,其特征为迟发型超敏反应受到抑制、抗体水平升高以及细胞毒性T淋巴细胞(CTL)活性启动。尽管接种于前房的P815细胞启动了CTL活性,但接种此类细胞的小鼠仍出现了逐渐生长的眼内肿瘤,因此我们研究了前房接种与皮下接种之间肿瘤生长模式的差异是否是由于前者细胞毒性反应异常且较弱所致。我们分析了接种P815细胞后脾脏中细胞毒性前体和效应细胞的裂解活性、靶标特异性及频率。我们的结果表明,P815接种的前房和皮下途径均产生了对P815肿瘤靶细胞具有同等裂解活性的脾脏CTL效应细胞。这些效应细胞对P815细胞具有高度特异性,不会裂解第三方EL-4靶标。对接受前房和皮下注射的动物脾脏和淋巴结中细胞毒性T细胞前体(pTc)频率的分析显示,两种途径产生的pTc频率相当。因此,置于前房的肿瘤细胞能够产生完整的细胞毒性前体和效应细胞,与皮下注射后产生的细胞毒性前体和效应细胞相当。所以,眼内肿瘤的逐渐生长不能归因于肿瘤特异性CTL反应的缺陷。

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