GH3 PITUITARY-ADENOMA CELLS CAN REVERSE THYMIC AGING IN RATS
GH3 PITUITARY-ADENOMA CELLS CAN REVERSE THYMIC AGING IN RATS
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DOI：
10.1073/pnas.83.15.5663
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发表时间：
1986-08-01
影响因子：
11.1
通讯作者：
WALKER, EB
中科院分区：
文献类型：
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作者：
KELLEY, KW;BRIEF, S;WALKER, EB
胸腺大小和T细胞功能随着年龄的增长而下降，并且还不可能完全逆转这种胸腺萎缩并完全恢复T细胞依赖的免疫功能。在这项研究中，GH 3垂体腺瘤细胞，分泌生长激素和催乳素，皮下植入16个月和22个月大的雌性Wistar-Furth大鼠和大鼠处死后约2个月。在未植入GH 3细胞的老龄大鼠中仅检测到胸腺残留，但在植入GH 3细胞的18月龄和24月龄大鼠中均发现胸腺。从GH 3植入18个月大的大鼠胸腺含有不同的皮质胸腺细胞和髓质上皮细胞。根据植物血凝素或伴刀豆球蛋白A的浓度，T细胞增殖反应的脾细胞从这些植入大鼠的2- 5倍大于18个月大的控制。在最佳浓度的有丝分裂原，增殖反应，无论是凝集素可以恢复到3个月大的Wistar-Furth女性脾细胞中观察到的水平。24个月大的GH 3植入大鼠胸腺含有更多的皮质胸腺细胞和更少的脂肪空泡比对照组，但他们没有完全重建。在24个月龄的对照大鼠中没有检测到显著的凝集素诱导的T细胞增殖反应或IL-2分泌，但是来自GH 3植入大鼠的脾细胞显示增强的T细胞增殖反应和增加的IL-2合成。胸腺细胞的增殖激活细胞分选仪分析显示，植入GH 3细胞的24月龄大鼠具有较高比例的Thy-1.1和辅助T细胞表型的淋巴细胞。这些数据表明，原位再生正常胸腺组织并逆转随着衰老发生的细胞介导的免疫力的自然丧失是可能的。
Thymic size and T-cell function decrease with age, and it has not yet been possible to totally reverse this thymic atrophy and completely restore T-cell-dependent immune functions. In this study, GH3 pituitary adenoma cells, which secrete growth hormone and prolactin, were implanted subcutaneously into 16- and 22-month-old female Wistar-Furth rats and the rats were sacrificed approximately 2 months later. Only thymic remnants were detected in aged, non-implanted rats, but thymus glands were found in both the 18- and the 24-month-old rats that had been implanted with GH3 cell. Thymus glands from the GH3-implanted 18-month-old rats contained distinct cortical thymocytes and medullary epithelial cells. Depending on the concentration of phytohemagglutinin or concanavalin A, T-cell proliferative responses of splenocytes from these implanted rats were 2- to 5-fold greater than those of 18-month-old controls. At the optimal concentration of mitogen, proliferative responses to either lectin could be restored to those levels observed in splenocytes from 3-month-old Wistar-Furth females. Thymus glands from 24-month-old GH3-implanted rats contained more cortical thymocytes and fewer fat vacuoles than controls, but they were not totally reconstituted. No significant lectin-induced T-cell proliferative responses or IL-2 secretion were detected in 24-month-old control rats, but splenocytes from GH3-implanted rats showed augmented T-cell proliferative responses and increased synthesis of IL-2. Fluorescence-activated cell-sorter analysis of thymocytes revealed that 24-month-old rats implanted with GH3 cells had a higher proportion of lymphocytes with the Thy-1.1 and helper-T-cell phenotypes. These data show that it is possible to regenerate normal thymic tissue in situ and reverse the natural loss in cell-mediated immunity that occurs with aging.