T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice
T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice
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T 细胞衍生的辅助因子可在 nu/nu 小鼠体内诱导细胞毒性 T 细胞
DOI：
10.1038/284278a0
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发表时间：
1980
期刊：
影响因子：
64.8
通讯作者：
K. Pfizenmaier
中科院分区：
文献类型：
--
作者：
H. Wagner;C. Hardt;K. Heeg;M. Röllinghoff;K. Pfizenmaier
T 细胞免疫能力和多样性被认为是在胸腺中产生的1,2。这一观点基于以下发现：(1) T 细胞个体发育依赖于胸腺3,4，(2) T 细胞相互作用的主要组织相容性限制在表型上与胸腺的 H-2 型相关5-9，以及 (3) H-2 相关免疫反应的表型表现与胸腺中选择的限制元件相似10-12。然而，尚不清楚被编程发育成T细胞的前胸腺细胞是否确实已经表达了受体多样性，也不清楚前胸腺细胞是否具有针对自身抗原发生反应的潜力，以及自我耐受机制是否是通过消除或抑制自身反应性克隆在胸腺中启动的。如果能够赋予前胸腺细胞抗原特异性效应功能，则可以更详细地分析胸腺对 T 细胞多样性和功能产生的影响。在小鼠中，裸突变缺乏功能性胸腺13,14； nu/nu 小鼠具有胸腺雏形，在胚胎中为上皮15，在成年时为纤维状、囊性残余物15,16；该残余物中没有淋巴细胞15-17。目前，nu/nu 小鼠中缺乏免疫活性 T 细胞的原因是胸腺前细胞缺乏胸腺分化和成熟（参见参考文献 13）。在这里，我们报告注射同种异体刺激细胞加上 Lyt 1 T 细胞衍生的辅助因子 18,19，称为白细胞介素 2（命名系统，参见参考文献 20），可以使 nu/nu 小鼠的淋巴细胞在体内分化为同种异体反应性细胞毒性 T 淋巴细胞 (CTL)。
T-cell immunocompetence and diversity are thought to be generated in the thymus1,2. This view is based on the findings that (1) T-cell ontogeny is thymus dependent3,4, (2) the major histocompatibility restrictions of T-cell interactions are phenotypically related to the H–2 type of the thymus5–9, and (3) the phenotypic manifestation of H–2-linked immune responsiveness parallels the restriction elements selected in thymus10–12. However, it is unclear whether pre-thymic cells programmed to develop into T cells do already express a receptor diversity, also whether pre-thymic cells have the potential to react against self-antigens, and whether the mechanism of self-tolerance is initiated in the thymus by either elimination or suppression of self-reactive clones. If it were possible to confer on pre-thymic cells antigen-specific effector functions, the impact of the thymus on the generation of T-cell diversity and function could be analysed in more detail. In mice, the nude mutation lacks a functioning thymus13,14; nu/nu mice possess a thymic rudiment which is epithelial in the embryo15 and a fibrous, cystic remnant in adult15,16; this remnant is not populated by lymphoid cells15–17. At present, the absence of immunocompetent T cells in nu/nu mice is explained by a lack of thymic differentiation and maturation of pre-thymic cells (reviewed in ref. 13). Here we report that injection of allogeneic stimulator cells plus a Lyt 1 T-cell-derived helper factor18,19, termed interleukin 2 (for the system of nomenclature, see ref. 20) allows lymphocytes of nu/nu mice to differentiate in vivo into alloreactive cytotoxic T lymphocytes (CTLs).