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生长激素和催乳素对小鼠T细胞发育及功能的不同作用。

Differential effects of growth hormone and prolactin on murine T cell development and function.

作者信息

Murphy W J, Durum S K, Longo D L

机构信息

Laboratory of Leukocyte Biology, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.

出版信息

J Exp Med. 1993 Jul 1;178(1):231-6. doi: 10.1084/jem.178.1.231.

Abstract

DW/J dwarf mice have a defect in their anterior pituitary and are deficient in growth hormone (GH) and prolactin (PRL). These mice have been demonstrated previously to have a deficiency in CD4/CD8 double-positive thymocytes, which could be corrected by treatment of these mice with recombinant human GH. Since PRL has been implicated in T cell function and human GH can interact with the PRL receptor, DW/J dwarf mice were treated with either ovine GH (ovGH) (20 micrograms/d) or ovine PRL (ovPRL) (20 micrograms/d). The ovine hormones can only bind their own specific receptors in the mouse. After several weeks of treatment, it was found that these two hormones produced markedly contrasting effects on T cells. Phenotypic analysis of the lymphoid organs was performed by flow cytometry and the functional capability of the peripheral T cells was assessed by immunizing the mice and determining the extent of antigen-specific proliferation of T cells obtained from the draining lymph nodes or by determining splenic mitogen responses. The results indicated that ovGH administration to dwarf mice resulted in significant increases in thymic cellularity yet had little effect on peripheral T cell responses. In contrast, the administration of ovPRL resulted in a further decrease in thymic cellularity when compared with untreated dwarf mice. No thymic effects of either ovGH or ovPRL administration were detected on the normal +/? counterparts. However, ovPRL administration resulted in a significant increase in the number and function of antigen-specific peripheral T cells in both immunized dwarf and +/? mice. The adjuvant effects of PRL occurred even though the mice also received complete Freund's adjuvant. These results suggest that neuroendocrine hormones may act in concert in T cell development. GH appears to promote thymocyte proliferation, while PRL appears to decrease thymus size and yet augment the number and function of antigen-specific T cells in the periphery.

摘要

DW/J 侏儒小鼠的垂体前叶存在缺陷,生长激素(GH)和催乳素(PRL)分泌不足。先前已证明这些小鼠的 CD4/CD8 双阳性胸腺细胞存在缺陷,用重组人生长激素治疗这些小鼠可纠正这一缺陷。由于催乳素与 T 细胞功能有关,且人生长激素可与催乳素受体相互作用,因此用绵羊生长激素(ovGH)(20 微克/天)或绵羊催乳素(ovPRL)(20 微克/天)对 DW/J 侏儒小鼠进行治疗。绵羊激素只能与小鼠体内自身的特异性受体结合。治疗数周后,发现这两种激素对 T 细胞产生了明显不同的影响。通过流式细胞术对淋巴器官进行表型分析,并通过免疫小鼠并确定从引流淋巴结获得的 T 细胞的抗原特异性增殖程度或通过测定脾细胞有丝分裂反应来评估外周 T 细胞的功能能力。结果表明,给侏儒小鼠注射 ovGH 可使胸腺细胞数量显著增加,但对外周 T 细胞反应影响不大。相比之下,与未治疗的侏儒小鼠相比,注射 ovPRL 导致胸腺细胞数量进一步减少。未检测到注射 ovGH 或 ovPRL 对正常 +/? 对照小鼠的胸腺有影响。然而,注射 ovPRL 使免疫的侏儒小鼠和 +/? 小鼠外周抗原特异性 T 细胞的数量和功能均显著增加。即使小鼠同时接受了完全弗氏佐剂,PRL 的佐剂作用仍然出现。这些结果表明,神经内分泌激素可能在 T 细胞发育过程中协同发挥作用。生长激素似乎促进胸腺细胞增殖,而催乳素似乎减小胸腺大小,但却增加外周抗原特异性 T 细胞的数量和功能。

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