DEVELOPMENT AND FUNCTION OF T-CELLS IN MICE RENDERED INTERLEUKIN-2 DEFICIENT BY GENE TARGETING

DEVELOPMENT AND FUNCTION OF T-CELLS IN MICE RENDERED INTERLEUKIN-2 DEFICIENT BY GENE TARGETING
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DOI:
10.1038/352621a0
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发表时间:
1991-08-15
期刊:
影响因子:
64.8
通讯作者:
HORAK, I
HORAK, I
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SCHORLE, H;HOLTSCHKE, T;HORAK, I

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白细胞介素-2(IL-2)是一种亲淋巴细胞激素,被认为在哺乳动物细胞的免疫应答中具有关键作用。它由活化的T淋巴细胞亚群产生,在体外作为主要的自分泌和旁分泌T细胞生长因子(综述见参考文献1-3)。然而,IL-2不是唯一的T细胞生长因子4,5,也不专门作用于T细胞,还促进NK细胞6的生长和B细胞7的分化。IL-2在T细胞发育中的作用已被假定,但仍存在争议8-12。在这里,我们测试的IL-2缺陷小鼠产生的靶向重组的IL的需求。我们发现,小鼠纯合子的IL-2基因突变是正常的胸腺细胞和外周T细胞亚群的组成,但表现为减少多克隆体外T细胞反应和血清免疫球蛋白的同种型水平的显着变化的免疫系统失调。
INTERLEUKIN-2 (IL-2) is a lymphocytotropic hormone which is thought to have a key role in the immune response of mammalian cells. It is produced by a subpopulation of activated T-lymphocytes and acts in vitro as the principal auto- and paracrine T-cell growth factor (for reviews see refs 1-3). IL-2 is, however, not the sole T-cell growth factor 4,5, nor does it act exclusively on T cells, also promoting growth of NK cells 6 and differentiation of B cells 7. A role for IL-2 in T-cell development has been postulated but remains controversial 8-12. Here we test the requirement for IL using IL-2-deficient mice generated by targeted recombination. We find that mice homozygous for the IL-2 gene mutation are normal with regard to thymocyte and peripheral T-cell subset composition, but that a dysregulation of the immune system is manifested by reduced polyclonal in vitro T-cell responses and by dramatic changes in the isotype levels of serum immunoglobulins.