Allo‐skin graft rejection, tumor rejection and natural killer activity in mice lacking p56lck

Allo‐skin graft rejection, tumor rejection and natural killer activity in mice lacking p56lck
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缺乏 p56lck 的小鼠的同种异体皮肤移植排斥、肿瘤排斥和自然杀伤活性

DOI:
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发表时间:
1995
影响因子:
5.4
通讯作者:
T. Mak
T. Mak
中科院分区:
医学3区
文献类型:
--
作者:
T. Wen;Li Zhang;S. Kung;T. Molina;Richard G. Miller;T. Mak

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缺乏p56lck分子(lck−/−)的小鼠胸腺细胞的成熟受到严重阻碍,并且外周成熟T细胞的数量大大减少。为了进一步分析lck−/−小鼠体内发育的T细胞的功能,我们评估了lck−/−小鼠排斥异体皮肤移植物和甲基胆蒽(MCA)诱导的同基因纤维肉瘤的能力,并检查了lck−/−自然杀伤(NK)细胞的生物活性。缺乏 p56lck 的小鼠无法排斥来自 MHC 不同或次要组织相容性不同的供体的皮肤移植物,即使它们已经用供体脾细胞进行了初始化。他们也未能排斥 MCA 诱导的免疫原性同基因纤维肉瘤 MC57X。缺乏 p56lck 的小鼠的 NK 活性正常,并且缺乏 p56lck 的小鼠及其免疫活性杂合子同窝小鼠之间,由聚(I)·聚(C)刺激或白介素-2 刺激(淋巴因子激活的杀伤细胞诱导)诱导的 NK 细胞活化没有差异。缺乏 p56lck 的 NK 细胞介导正常的抗体依赖性细胞介导的细胞毒性 (ADCC) 反应。这项研究的结果表明,p56lck 的缺失会严重损害免疫系统的效应器,从而介导同种异体皮肤移植物和同种肿瘤的排斥反应。 lck −/− 小鼠中的正常 NK 活性表明 NK 细胞的发育和激活不需要 p56lck。
Mice lacking the p56lck molecule (lck−/−) have a profound block in the maturation of thymocytes and a greatly reduced number of peripheral mature T cells. To analyze further the functions of the T cells developed in lck −/− mice in vivo, we evaluated the ability of lck−/− mice to reject allo‐skin grafts and methylcholanthrene (MCA)‐induced syngeneic fibrosarcoma, and also examined the biological activity of lck −/− natural killer (NK) cells. Mice lacking p56lck failed to reject skin grafts from either MHC‐disparate or minor‐histocompatibility‐different donors, even after they had been primed with donor spleen cells. They also failed to reject the MCA‐induced immunogenic syngeneic fibrosarcoma, MC57X. NK activity in mice lacking p56lck was normal, and there were no differences in the NK cell activation induced by poly(I) · poly(C) stimulation or interleukin‐2 stimulation (lymphokine‐activated killer induction) between mice lacking p56lck and their immunocompetent heterozygous littermates. NK cells lacking p56lck mediated a normal antibody‐dependent cell‐mediated cytotoxicity (ADCC) response. The results of this study indicate that the loss of p56lck severely impairs the effectors of the immune system which mediate the rejection of allo‐skin grafts and syngeneic tumors. The normal NK activity in lck −/− mice suggests that p56lck is not required for the development and activation of NK cells.
DOI: 10.1126/science.1465616
发表时间: 1992-12-11
期刊: SCIENCE
影响因子: 56.9
作者:
MIZOGUCHI, H;O'SHEA, JJ;OCHOA, AC
通讯作者: OCHOA, AC
DOI: --
发表时间: 1993-12
期刊: Cancer research
影响因子: 11.2
作者:
J. Finke;A. Zea;J. Stanley;D. Longo;H. Mizoguchi;R. Tubbs;R. Wiltrout;J. O’Shea;S. Kudoh
通讯作者: J. Finke;A. Zea;J. Stanley;D. Longo;H. Mizoguchi;R. Tubbs;R. Wiltrout;J. O’Shea;S. Kudoh