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体内白细胞介素-2(IL-2)治疗后,CD56⁺自然杀伤细胞上白细胞介素-2(IL-2)受体β链(p70)表达增加:p70表达不能单独预测中等亲和力IL-2结合水平。

Increased expression of the interleukin 2 (IL-2) receptor beta chain (p70) on CD56+ natural killer cells after in vivo IL-2 therapy: p70 expression does not alone predict the level of intermediate affinity IL-2 binding.

作者信息

Voss S D, Robb R J, Weil-Hillman G, Hank J A, Sugamura K, Tsudo M, Sondel P M

机构信息

Department of Human Oncology, University of Wisconsin, Madison 53792.

出版信息

J Exp Med. 1990 Oct 1;172(4):1101-14. doi: 10.1084/jem.172.4.1101.

Abstract

The expression of the 70-kD beta subunit of the interleukin 2 receptor (IL-2R) has been examined on peripheral blood lymphocytes (PBL) obtained from patients receiving systemic infusions of IL-2. Using monoclonal antibodies directed against p70, flow cytometric analyses revealed a greater than threefold increase in expression of the IL-2R beta chain on CD56+ natural killer (NK) cells from post-IL-2 therapy PBL relative to pre-therapy cells. The level of p70 expression on the post-therapy cells was three- to fourfold greater (based on fluorescence intensity) than the level of p70 expression on YT cells, an NK-like cell line that expresses approximately 12,000 intermediate affinity IL-2 binding sites/cell. Despite the high level of p70 expression, in 125I-IL-2 binding assays only 790-1,290 intermediate affinity IL-2 binding sites/cell were detected on post-therapy cells from six patients. These data represent the first report of increased p70 expression after in vivo IL-2 administration and suggest a requirement for at least one additional subunit for the formation of functional intermediate affinity IL-2Rs. Furthermore, the presence on the surface of post-therapy NK cells of excess p70 that does not bind IL-2 with intermediate affinity implies that the formation of intermediate affinity IL-2Rs is not solely determined by the level of p70 expression, and that the response of NK cells to IL-2 might be regulated by altering the expression of p70 or some other IL-2R subunit.

摘要

对接受白细胞介素2(IL-2)全身输注患者外周血淋巴细胞(PBL)上白细胞介素2受体(IL-2R)70-kDβ亚基的表达进行了检测。使用针对p70的单克隆抗体,流式细胞术分析显示,与治疗前细胞相比,IL-2治疗后PBL中CD56 +自然杀伤(NK)细胞上IL-2Rβ链的表达增加了三倍以上。治疗后细胞上p70的表达水平(基于荧光强度)比YT细胞(一种表达约12,000个中等亲和力IL-2结合位点/细胞的NK样细胞系)上p70的表达水平高三至四倍。尽管p70表达水平很高,但在125I-IL-2结合试验中,在6名患者治疗后的细胞上仅检测到790-1,290个中等亲和力IL-2结合位点/细胞。这些数据代表了体内给予IL-2后p70表达增加的首次报道,并表明功能性中等亲和力IL-2R的形成至少需要一个额外的亚基。此外,治疗后NK细胞表面存在过量的p70,其不与中等亲和力的IL-2结合,这意味着中等亲和力IL-2R的形成不仅仅由p70表达水平决定,并且NK细胞对IL-2的反应可能通过改变p70或其他一些IL-2R亚基的表达来调节。

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