Altered proliferative response by T lymphocytes of Ly-6A (Sca-1) null mice.

Altered proliferative response by T lymphocytes of Ly-6A (Sca-1) null mice.
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LY-6A(SCA-1)无效小鼠的T淋巴细胞的增殖反应改变了。

DOI:
10.1084/jem.186.5.705
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发表时间:
1997-08-29
影响因子:
15.3
通讯作者:
Flood, P M
Flood, P M
中科院分区:
医学1区
文献类型:
--
作者:
Stanford, W L;Haque, S;Alexander, R;Liu, X;Latour, A M;Snodgrass, H R;Koller, B H;Flood, P M

文献摘要

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Ly-6A是一种鼠抗原,其涉及淋巴细胞活化并可能涉及造血干细胞的活化。抗体交联研究和反义实验表明,Ly-6A是淋巴细胞共激活分子。为了更好地理解Ly-6A的功能,我们使用基因靶向来产生Ly-6A缺失小鼠,这些小鼠是健康的并且具有正常数量和百分比的造血谱系。然而,从Ly-6A缺陷的动物T淋巴细胞增殖在一个显着更高的速度比野生型同窝小鼠的抗原和有丝分裂原的反应。此外,当与同种异体抗原共培养时,与野生型脾细胞相比,Ly-6A突变体脾细胞产生更多的细胞毒性T淋巴细胞。这种增强的增殖不是由于反应动力学、对刺激物浓度的敏感性或T细胞群的细胞因子产生的改变,而是在体内和体外T细胞反应中表现出来。此外,来自Ly-6A缺陷动物的T细胞表现出对抗原刺激的延长的增殖反应,从而表明Ly-6A起到下调淋巴细胞反应的作用。
Ly-6A is a murine antigen which is implicated in lymphocyte activation and may be involved in activation of hematopoietic stem cells. Antibody cross-linking studies and antisense experiments have suggested that Ly-6A is a lymphocyte coactivation molecule. To better understand the function of Ly-6A, we used gene targeting to produce Ly-6A null mice which are healthy and have normal numbers and percentages of hematopoietic lineages. However, T lymphocytes from Ly-6A–deficient animals proliferate at a significantly higher rate in response to antigens and mitogens than wild-type littermates. In addition, Ly-6A mutant splenocytes generate more cytotoxic T lymphocytes compared to wild-type splenocytes when cocultured with alloantigen. This enhanced proliferation is not due to alterations in kinetics of response, sensitivity to stimulant concentration, or cytokine production by the T cell population, and is manifest in both in vivo and in vitro T cell responses. Moreover, T cells from Ly-6A–deficient animals exhibit a prolonged proliferative response to antigen stimulation, thereby suggesting that Ly-6A acts to downmodulate lymphocyte responses.