Regulation of lymphokine-activated killer activity and pore-forming protein gene expression in human peripheral blood CD8+ T lymphocytes. Inhibition by transforming growth factor-beta.
Regulation of lymphokine-activated killer activity and pore-forming protein gene expression in human peripheral blood CD8+ T lymphocytes. Inhibition by transforming growth factor-beta.
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DOI：
10.4049/jimmunol.146.10.3289
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发表时间：
1991-05
影响因子：
4.4
通讯作者：
M. Smyth;S. Strobl;H. Young;J. Ortaldo;A. Ochoa
中科院分区：
文献类型：
--
作者：
M. Smyth;S. Strobl;H. Young;J. Ortaldo;A. Ochoa
研究了转化生长因子-β 1（TGF-β）对活化诱导的CD 8 + T细胞细胞毒性和基因表达的影响。在与IL-2和OKT 3 mAb一起培养6至18天的CD 8 + T细胞中，TGF-β被证明可抑制孔形成蛋白（PFP）mRNA表达和总苯甲酰氧羰基-L-赖氨酸硫代苄酯酶活性。结论：在TGF-β存在或不存在的情况下，CD 8 + T细胞的PFP mRNA表达与LAK活性密切相关。TGF-β对CD 8 + T细胞PFP mRNA表达和LAK活性的抑制作用可通过从培养物中去除TGF-β而逆转。淋巴因子、粘附/识别分子和活化的p55 IL-2 R的表达，以前与细胞毒性淋巴细胞的溶解机制有关，要么检测不到，要么与TGF-β抑制LAK活性无关。此外，与效应/靶细胞结合无关，IL-2/OKT 3 mAb激活的CD 8 + T细胞的凝集素或杂合抗体依赖性细胞毒性通过与TGF-β预培养而被抑制。TGF-β还抑制静息T细胞中PFP mRNA的快速活化诱导表达和细胞毒性潜力，从而表明TGF-β的作用不依赖于T细胞增殖。TGF-β对CD 8 + T细胞PFP mRNA表达和细胞毒性潜力的抑制具有TGF-β剂量依赖性;然而，各种活化刺激物（包括IL-2、IL-6和OKT 3 mAb）均受到TGF-β类似的抑制。因此，TGF-β可能是CD 8 + T细胞细胞毒性功能的重要一般调节因子，特别是通过抑制PFP（一种与细胞毒性淋巴细胞的溶解功能有关的主要溶细胞蛋白）的表达。
The effect of transforming growth factor-beta 1 (TGF-beta) on activation-induced CD8+ T cell cytotoxicity and gene expression was investigated. TGF-beta was demonstrated to inhibit pore-forming protein (PFP) mRNA expression and total benzoyloxycarbonyl-L-lysine thiobenzyl ester esterase activity in CD8+ T cells cultured with IL-2 and OKT3 mAb for 6 to 18 days. Consistently, in the absence or presence of TGF-beta, the PFP mRNA expression and lymphokine-activated killer (LAK) activity of CD8+ T cells were closely correlated. The inhibitory effects of TGF-beta on both CD8+ T cell PFP mRNA expression and LAK activity were reversible by removal of TGF-beta from the culture. Expression of lymphokines, adhesion/recognition molecules, and activated p55 IL-2R, previously implicated in the lytic mechanism of cytotoxic lymphocytes, either was not detectable or did not correlate with TGF-beta inhibition of LAK activity. In addition, independently of effector/target cell binding, the lectin- or heteroconjugated antibody-dependent cellular cytotoxicity of IL-2/OKT3 mAb-activated CD8+ T cells was inhibited by preculture with TGF-beta. TGF-beta also inhibited the rapid activation-induced expression of PFP mRNA and cytotoxic potential in resting T cells, thereby indicating that the effect of TGF-beta was independent of T cell proliferation. TGF-beta inhibition of CD8+ T cell PFP mRNA expression and cytotoxic potential was TGF-beta dose dependent; however, a variety of activation stimuli (including IL-2, IL-6, and OKT3 mAb) were all similarly inhibited by TGF-beta. Therefore, TGF-beta may be an important general regulator of CD8+ T cell cytotoxic function, in particular by suppressing expression of PFP, a major cytolytic protein implicated in the lytic function of cytotoxic lymphocytes.