Rolstad B, Fossum S
Anatomical institute, University of Oslo, Norway.
Anat Embryol (Berl). 1990;181(3):215-26. doi: 10.1007/BF00174616.
The athymic nude (rnu) rat lacks a functional thymus and normal alloreactive T cells. These animals, therefore, have been widely used as tools for studying thymus-independent immune responses. The absence of functional T cells would, to most investigators, indicate that these rats have a defective cellular immune defence. However, although rnu rats accept organ allografts infinitely, they are nevertheless capable of rejecting allografts consisting of lymphocytes or bone marrow cells with increased vigour, and this via antibody-independent mechanisms. These rejection phenomena have operationally been termed allogeneic lymphocyte cytotoxicity (ALC) and allogeneic bone marrow cell cytotoxicity (ABC). Unlike organ allograft immunity this kind of rejection requires no presensitization of the recipient and is surprisingly rapid: it commences within a few hours of i.v. injection of the allogeneic cells and is usually complete by 24 h. Moreover, products coded for by genes within, or closely linked to the major histocompatibility complex (MHC), are clearly involved in the interaction between effector and target cells, as grafted cells from MHC-congenic rat strains are vigorously rejected. In contrast to the defective T cell immune responses in athymic nude rats, the natural killer (NK) cell function is not impaired, and it has been suggested that the spontaneous rejection of MHC-incompatible lymphohematopoietic cells is in fact mediated by NK cells. If the MHC antigens themselves serve as targets in this kind of allorejection, this hypothesis is in apparent contrast with the prevailing view that recognition by NK cells is not guided by, or directed against, MHC-antigens on the target cell surface. Aging athymic nude mice and rats generate cells that rearrange and express T cell receptor (TCR) genes, and this has raised the possibility that T cells or T-like cells in athymic nude animals are responsible for ALC and ABC. This possibility urged the device of an in vitro test system for identification and further characterization of the effector cells in these rejection phenomena. Under appropriate conditions, cells from the rnu rat spleen or liver with natural killer function, i.e. the ability to lyse certain kinds of tumor cells in vitro, are also spontaneously cytotoxic for allogeneic small lymphocytes and bone marrow cells in vitro. Furthermore, these cells can be grown in vitro in the presence of interleukin 2 (IL-2) to generate populations of lymphokine-activated killer (LAK) cells, and these cells have the same spectrum of alloreactivity in ALC and ABC as the native NK cells.(ABSTRACT TRUNCATED AT 250 WORDS)
无胸腺裸（rnu）大鼠缺乏功能性胸腺和正常的同种异体反应性T细胞。因此，这些动物已被广泛用作研究非胸腺依赖性免疫反应的工具。对大多数研究人员来说，功能性T细胞的缺失表明这些大鼠的细胞免疫防御存在缺陷。然而，尽管rnu大鼠能无限期接受器官异体移植，但它们仍能以更强的活力通过与抗体无关的机制排斥由淋巴细胞或骨髓细胞组成的异体移植。这些排斥现象在操作上被称为同种异体淋巴细胞细胞毒性（ALC）和同种异体骨髓细胞细胞毒性（ABC）。与器官异体移植免疫不同，这种排斥不需要受体预先致敏，而且速度惊人：在静脉注射异体细胞后的几个小时内就开始了，通常在24小时内完成。此外，主要组织相容性复合体（MHC）内或与之紧密连锁的基因编码的产物显然参与了效应细胞与靶细胞之间的相互作用，因为来自MHC同基因大鼠品系的移植细胞会被强烈排斥。与无胸腺裸大鼠中缺陷的T细胞免疫反应相反，自然杀伤（NK）细胞功能并未受损，有人提出MHC不相容的淋巴造血细胞的自发排斥实际上是由NK细胞介导的。如果MHC抗原本身在这种同种异体排斥中作为靶标，那么这个假设显然与普遍观点相反，即NK细胞的识别不是由靶细胞表面的MHC抗原引导或针对它们的。衰老的无胸腺裸小鼠和大鼠会产生重排并表达T细胞受体（TCR）基因的细胞，这增加了无胸腺裸动物中的T细胞或T样细胞对ALC和ABC负责的可能性。这种可能性促使人们设计一种体外测试系统，用于识别和进一步表征这些排斥现象中的效应细胞。在适当条件下，来自rnu大鼠脾脏或肝脏的具有自然杀伤功能（即体外裂解某些类型肿瘤细胞的能力）的细胞，对体外的同种异体小淋巴细胞和骨髓细胞也具有自发细胞毒性。此外，这些细胞可以在白细胞介素2（IL-2）存在的情况下在体外生长，以产生淋巴因子激活的杀伤（LAK）细胞群体，并且这些细胞在ALC和ABC中的同种异体反应谱与天然NK细胞相同。（摘要截选至250词）
