A role for elevated H-2 antigen expression in resistance to neoplasia caused by radiation-induced leukemia virus. Enhancement of effective tumor surveillance by killer lymphocytes
A role for elevated H-2 antigen expression in resistance to neoplasia caused by radiation-induced leukemia virus. Enhancement of effective tumor surveillance by killer lymphocytes
复制标题
H-2 抗原表达升高在抵抗由辐射诱导的白血病病毒引起的肿瘤中的作用。
DOI：
--
复制
发表时间：
1979
影响因子：
15.3
通讯作者：
Meruelo
中科院分区：
文献类型：
--
作者：
Daniel B;Meruelo
对辐射诱导的白血病病毒（RadLV）引起的瘤形成的抗性是由主要组织相容性复合体H-2D区域的基因介导的。先前的观察表明，在病毒接种后立即可检测到H-2抗原的细胞合成和细胞表面表达的快速增加，这表明H-2抗原表达的改变可能在宿主防御病毒感染的机制中起重要作用。这一概念得到以下意见的支持。首先，当H-2阳性靶细胞用于细胞介导的淋巴溶解（CML）测定时，可以容易地检测针对RadLV转化或感染的细胞的细胞介导的免疫。（尽管从明显患有白血病的动物中获得并维持在组织培养物中的RadLV转化细胞是H-2阴性的，但这些细胞可以通过在正常动物体内传代来恢复其H-2表型。H-2阴性细胞是CML测定中的不良靶。）第二，抗性小鼠在感染RadLV时比易感小鼠产生更多的效应子。第三，将正常（未感染的）胸腺细胞注射到耐药或敏感H-2型的同基因受体中不会刺激CML反应。然而，注射来自抗性小鼠的RadLV感染的胸腺细胞产生强烈的CMI反应，并且当H-2和病毒抗原表达升高时，这种胸腺细胞引起最强的反应。相比之下，注射易感小鼠的感染胸腺细胞（表达病毒抗原，但H-2抗原水平较低）不会刺激CML反应。这些发现可能解释了许多研究者发现的当病毒接种到新生小鼠时更容易诱导白血病以及某些致癌的C型RNA病毒的优先胸腺嗜性。表达非常低水平H-2的细胞，如胸腺细胞，可能作为病毒感染的容许靶点，因为它们缺乏触发防御性宿主免疫应答所需的双重或改变的识别信号的重要组分（H-2抗原）。
Resistance to neoplasia caused by radiation-induced leukemia virus (RadLV) is mediated by gene(s) in the H-2D region of the major histocompatibility complex. The previous observation that rapid increases in cellular synthesis and cell-surface expression of H-2 antigens are detectable immediately after virus inoculation has suggested that altered expression of H-2 antigens may play a significant role in the mechanism(s) of host defense to virus infection. This concept is supported by the following observations. First, cell-mediated immunity against RadLV transformed or infected cells can be detected with ease when H-2-positive target cells are used in the cell-mediated lympholysis (CML) assay. (Although RadLV transformed cells obtained from overtly leukemic animals and maintained in tissue culture are H-2 negative, these cells can regain their H-2 phenotype by in vivo passage in normal animals. The H-2-negative cells are poor targets in a CML assay.) Second, resistant mice develop greater numbers of effectors when infected with RadLV than do susceptible mice. Third, injection of normal (uninfected) thymocytes into syngeneic recipients of resistant or susceptible H-2 type does not stimulate a CML response. However, injection of RadLV infected thymocytes from resistant mice produces a vigorous CMI response, and such thymocytes elicit the strongest response at a time when both H-2 and viral antigen expression is elevated. By contrast, injection of infected thymocytes from susceptible mice, which express viral antigens, but low levels of H-2 antigens, does not stimulate a CML reaction. These findings may explain the easier induction of leukemia found by many investigators when virus is inoculated into neonatal mice and the preferential thymus tropism of some oncogenic type-C RNA virus. Cells expressing very low levels of H-2, such as thymocytes, may serve as permissive targets for virus infection because they lack an important component (H-2 antigens) of the dual or altered recognition signal required to trigger a defensive host immune response.