Gaufo G O, Diamond M C
Group in Endocrinology, University of California, Berkeley 94720-3140, USA.
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4165-9. doi: 10.1073/pnas.93.9.4165.
One distinctive effect on T-cell development was analyzed by selectively increasing serum prolactin (PRL) concentration in thymus-grafted congenitally athymic nude mice and by neutralizing PRL in suspension cultures of thymus from 1-day-old neonatal mice. Flow cytometric analysis of single-positive CD4+ and CD8+ cells derived from inguinal lymph nodes revealed a CD4/CD8 cell ratio of 2.2 +/- 0.18 (mean +/- SEM) in thymus-grafted nude mice that is similar to the ratio for immune-competent BALB/c mice (2.0 +/- 0.06). Addition of the pituitary to thymus-grafted nude mice significantly elevated serum PRL (P < 0.005) and increased the CD4/CD8 cell ratio (2.8 +/- 0.12; P < 0.005), demonstrating preferential stimulation of CD4+ cell development. T cells in nude mice receiving sham (submandibular salivary gland) or pituitary grafts alone were below detectable levels. Suspension cultures of neonatal thymus treated with anti-mouse PRL antiserum resulted in 20% and 30% decreases in double-positive CD4+8+ thymocytes and thymocyte viability, respectively. A 10-fold increase in double-negative CD4-8- thymocytes expressing the interleukin 2 receptor alpha chain, CD25, was also observed concurrently. Our findings illustrate an important way in which PRL may participate in two interrelated mechanisms: the regulation of peripheral single-positive cells and the maintenance of thymocyte viability during the double-positive stage of intrathymic differentiation.
通过选择性提高移植胸腺的先天性无胸腺裸鼠血清催乳素(PRL)浓度,以及在1日龄新生小鼠胸腺的悬浮培养物中中和PRL,分析了对T细胞发育的一种独特影响。对来自腹股沟淋巴结的单阳性CD4⁺和CD8⁺细胞进行流式细胞术分析发现,移植胸腺的裸鼠中CD4/CD8细胞比率为2.2±0.18(平均值±标准误),这与免疫健全的BALB/c小鼠的比率(2.0±0.06)相似。给移植胸腺的裸鼠添加垂体显著提高了血清PRL(P<0.005),并增加了CD4/CD8细胞比率(2.8±0.12;P<0.005),表明对CD4⁺细胞发育有优先刺激作用。仅接受假手术(下颌下唾液腺)或垂体移植的裸鼠中的T细胞低于可检测水平。用抗小鼠PRL抗血清处理新生胸腺的悬浮培养物,分别导致双阳性CD4⁺8⁺胸腺细胞和胸腺细胞活力降低20%和30%。同时还观察到表达白细胞介素2受体α链CD25的双阴性CD4⁻8⁻胸腺细胞增加了10倍。我们的研究结果说明了PRL可能参与两种相关机制的一种重要方式:对外周单阳性细胞的调节以及在胸腺内分化的双阳性阶段维持胸腺细胞活力。