CONTROLS OF PROLIFERATION SPECIFIC FOR LEUKEMIAS

本项目是一项研究自然和诱导小鼠对 造血肿瘤的增殖。 调查的重点是 免疫生物学和效应系统异质性; 机制，并对遗传控制的反应，目标决定因素， 以及效应细胞和调节细胞群的分化。 的 造血组织相容性（Hh）和/或主要 组织相容性复合体（H-2）基因产物在正常人 造血干细胞和白血病淋巴瘤细胞是核心的 由于淋巴细胞识别这些结构， 系统导致体内靶细胞的抑制和/或排斥（即， 杂交和同种异体抗性）和体外细胞毒性（即， 初级F1 抗亲本细胞介导的淋巴细胞溶解）。 重点将 不仅放置在Hh/H-2控制的结构上， 作为小鼠对自体免疫反应的靶点的结构 或同源肿瘤。 这种“自身反应性”是由效应子介导的 属于自然杀伤细胞（NK）和细胞毒性T淋巴细胞（CTL） 班 辐射F对亲代淋巴瘤移植物的抵抗1 混合 小鼠涉及未鉴定的效应器机制，部分为NK样（效应器 不需要诱导，并且是相对抗辐射的，不依赖于胸腺， 受干扰素调节），但识别特定的Hh/H-2基因产物， 在18至96小时内引起移植物排斥。 体外激活 F1 抗亲本CTL涉及不同的机制，因为应答细胞 必须受到刺激，并且是辐射敏感的以及胸腺依赖性的。 F1 抗亲本CTL识别基因的产物， 在某些单倍型和菌株中与Hh基因不可区分，但 根据重组分析，在其他方面可区分。 （LB）

This project is a study of natural and induced resistance of mice to the proliferation of hemopoietic tumors. The investigations are focused on the immunobiology and heterogeneity of effector systems; on regulatory mechanisms, and on genetic controls of responsiveness, target determinants, and differentiation of effector and regulatory cell populations. The identity of hemopoietic-histocompatibility (Hh) and/or major histocompatibility complex (H-2) gene products expressed on normal hemopoietic stem cells and leukemia-lymphoma cells is central to the project since recognition of these structures by cells of the lymphoid system leads to inhibition and/or rejection of target cells in vivo (i.e., hybrid and allogeneic resistance) and to cytotoxicity in vitro (i.e., primary F1 antiparent cell-mediated lympholysis). Emphasis will be placed not only on Hh/H-2-controlled structures but also on other cellular structures that serve as targets for mouse reactivities against autologous or syngeneic tumors. Such "autoreactivities" are mediated by effectors belonging to the natural killer (NK) and cytotoxic T lymphocyte (CTL) classes. Resistance to parental lymphoma grafts by irradiated F1 hybrid mice involves unidentified effector mechanisms, in part NK-like (effectors need not be induced and are relatively radioresistant, thymus independent, modulated by interferon), yet recognizing specific Hh/H-2 gene products and causing graft rejection within 18 to 96 hrs. The in vitro activation of F1 antiparent CTL involves different mechanisms, since responder cells must be stimulated and are radiosensitive as well as thymus dependent. F1 antiparent CTL recognize the products of genes that are indistinguishable from Hh genes in certain haplotypes and strains but are distinguishable in others according to recombinant analysis. (LB)