Effects of overexpression of growth hormone on T cell activity in transgenic mice.
Effects of overexpression of growth hormone on T cell activity in transgenic mice.
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生长激素过度表达对转基因小鼠 T 细胞活性的影响。
DOI：
10.1007/bf03179853
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发表时间：
2002
影响因子：
3.4
通讯作者：
Bartke,A
中科院分区：
文献类型：
--
作者：
Esquifino,AI;Arce,A;Alvarez,MP;Szary,A;Brown-Borg,H;Bartke,A
生长激素在免疫反应的成熟和维持中起着关键作用，然而，长期高循环浓度的激素对免疫系统的影响知之甚少。使用过表达牛生长激素（b-GH）基因（与大鼠磷酸烯醇式丙酮酸羧激酶启动子（PEPCK）融合）的转基因小鼠，其异源b-GH的血浆浓度非常高，以及其同窝正常同胞。在2月龄和6月龄的雄性转基因小鼠和正常同窝小鼠中检测脾细胞构成、总T淋巴细胞百分比、CD 4+和CD 8+细胞百分比、T细胞亚群比率、丝裂原诱导的淋巴细胞增殖和自然杀伤（NK）细胞活性。在两个年龄段，转基因小鼠的脾淋巴细胞数量均大于匹配的正常同窝小鼠。转基因小鼠的NK细胞活性在两个年龄段都低于匹配的正常同窝小鼠，在老年小鼠中发现的最低值。b-GH转基因小鼠在两个年龄段的T细胞百分比均较低，然而，与正常对照组相比，在年轻的转基因小鼠中，CD 4+细胞百分比降低，而CD 8+细胞百分比增加。PEPCK-b-GH-25小鼠脾细胞的基础和丝裂原诱导的增殖能力与两个年龄的正常同窝小鼠相比均降低。与同窝对照组或较年轻的小鼠相比，6月龄PEPCK-b-GH-25小鼠对伴刀豆球蛋白A和植物血凝素的应答指数显著降低。这些结果表明，小鼠中b-GH的过度表达与T细胞功能下降有关，并且这些异常是年龄依赖性的。
Growth hormone plays a key role in the maturation and maintenance of the immune response, however, the effects of chronic high circulating concentrations of the hormone on the immune system is poorly understood. Transgenic mice overexpressing bovine growth hormone (b-GH) gene, fused to the rat phosphoenolpyruvate carboxykinase promoter (PEPCK), with very high plasma concentration of heterologous b-GH and their littermate normal siblings were used. Spleen cellularity, percentages of total T lymphocytes, CD4+ and CD8+ cells, ratio of T cell subpopulations, mitogen-induced lymphocyte proliferation and natural killer (NK) cell activity were examined in male transgenic mice and normal littermate mice at 2 and 6 months of age. The number of splenic lymphocytes was greater in transgenic mice than in matched normal littermates at both ages. The NK cell activity was lower in transgenic mice than in the matched normal littermates at both ages, with the lowest values found in older mice. The b-GH transgenic mice had lower percentages of T cells at both ages, however, in young transgenic mice, the percentage of CD4+ cells was reduced while percentage of CD8+ cells was increased in comparison to normal controls. Both basal and mitogen-induced proliferation capacity of splenocytes were reduced in PEPCK-b-GH-25 mice as compared to normal littermates of both ages. Proliferative indexes in response to concanavalin A and phytohemagglutinin were markedly decreased in 6 month old PEPCK-b-GH-25 mice as compared to littermate controls or younger mice. These results indicate that overexpression of b-GH in mice is associated with decreased T cell function and that these abnormalities are age-dependent.