Roberts L K
J Immunol. 1986 Mar 1;136(5):1908-16.
Ultraviolet radiation (UV) is a potent carcinogen for the induction of skin tumors. In this regard, UV represents a unique carcinogenic agent, in that depending on the dosage and conditions of administration it can function as either a complete carcinogen, a carcinogenic promoting agent, or an immunologic modulator of anti-tumor rejection responses. The immunologic modulatory activity of UV has been demonstrated in numerous studies. These studies have shown that subcarcinogenic doses of UV induce a population of suppressor T lymphocytes (Ts cells) that allow for the emergence and progression of UV-induced tumors. Although the phenotypic and functional properties of these cells have been established, it was unclear as to whether the UV-induced Ts cell population consisted of multiple Ts cell clones able to recognize a range of unique tumor antigens or a limited number of Ts cell clones with functional specificity directed toward a common tumor-associated antigen (TAA). To address this question, an interleukin 2-dependent, UV-induced cloned Ts cell line was derived, by limiting dilution without exogenous antigen stimulation, from the splenic T cell population of a C3H mouse that had been exposed to a subcarcinogenic dose of UV. This Ts cell line, designated UV2.10, was selected for its ability to suppress the in vitro differentiation of cytotoxic T cells from the draining lymph nodes of UV-induced tumor-immune mice. When transferred into non-UV-irradiated syngeneic mice, which normally reject a UV-induced tumor implant, the UV2.10 cells rendered their hosts susceptible to the growth of a battery of UV-induced tumors. Although capable of suppressing in vitro and in vivo UV-induced tumor-immune responses, UV2.10 cells did not inhibit the elicitation of contact hypersensitivity responses, the rejection of allogeneic skin grafts, responses, the rejection of allogeneic skin grafts, or the rejection of allogeneic UV-induced tumors. These data suggest that the cloned UV2.10 Ts cell line possesses functional antigenic specificity that may be limited to the regulation of immune responses that are directed toward the TAA expressed by syngeneic UV-induced tumors. Employing monoclonal antibodies and FACS analysis, the cell surface phenotype of the UV2.10 cell line was determined to be: Thy-1.2+, Lyt-1-, Lyt-2+/- (dim), L3T4a-, I-A/E-, and I-J+. This cell surface phenotype is indicative of a suppressor T cell. These data lend further support to the hypothesis that the UV-induced Ts cell population is clonal in nature and functions through its ability to recognize a common TAA(s) that appears to be expressed by virtually all UV-induced tumors.
紫外线辐射（UV）是诱导皮肤肿瘤的一种强效致癌物。在这方面，UV是一种独特的致癌剂，因为根据剂量和给药条件，它既可以作为完全致癌物、致癌促进剂，也可以作为抗肿瘤排斥反应的免疫调节剂。UV的免疫调节活性已在众多研究中得到证实。这些研究表明，亚致癌剂量的UV可诱导一群抑制性T淋巴细胞（Ts细胞）的产生，这些细胞使得UV诱导的肿瘤得以出现和发展。尽管这些细胞的表型和功能特性已经明确，但尚不清楚UV诱导的Ts细胞群体是由多个能够识别一系列独特肿瘤抗原的Ts细胞克隆组成，还是由数量有限的、针对共同肿瘤相关抗原（TAA）具有功能特异性的Ts细胞克隆组成。为了解决这个问题，通过有限稀释法，在无外源性抗原刺激的情况下，从暴露于亚致癌剂量UV的C3H小鼠的脾T细胞群体中获得了一种依赖白细胞介素2的、UV诱导的克隆Ts细胞系。这个Ts细胞系被命名为UV2.10，它之所以被选中，是因为它能够抑制UV诱导的肿瘤免疫小鼠引流淋巴结中细胞毒性T细胞的体外分化。当将UV2.10细胞转移到未接受UV照射的同基因小鼠体内时（这些小鼠通常会排斥UV诱导的肿瘤植入物）这些细胞使得它们的宿主易受一系列UV诱导肿瘤的生长影响。尽管UV2.10细胞能够在体外和体内抑制UV诱导的肿瘤免疫反应，但它们并不抑制接触性超敏反应的激发、同种异体皮肤移植的排斥反应或同种异体UV诱导肿瘤的排斥反应。这些数据表明，克隆的UV2.10 Ts细胞系具有功能性抗原特异性，可能仅限于调节针对同基因UV诱导肿瘤所表达的TAA的免疫反应。利用单克隆抗体和荧光激活细胞分选分析，确定UV2.10细胞系的细胞表面表型为：Thy-1.2+、Lyt-1-、Lyt-2+/-（弱阳性）、L3T4a-、I-A/E-和I-J+。这种细胞表面表型表明它是一种抑制性T细胞。这些数据进一步支持了这样一种假说，即UV诱导的Ts细胞群体本质上是克隆性的，并且通过其识别几乎所有UV诱导肿瘤似乎都表达的共同TAA的能力发挥作用。
