Bouchard B, Ormandy C J, Di Santo J P, Kelly P A
Institut National de la Santé et de la Recherche Médicale U-344, Endocrinologie Moléculaire, Faculté de Médecine Necker, Paris, France.
J Immunol. 1999 Jul 15;163(2):576-82.
Prolactin (PRL) is the primary lactogenic pituitary hormone that plays an essential role in many aspects of reproduction, from fertilization to mammary gland development and maternal behavior. PRL has also been reported to play a role in immunoregulation. Because initial observations indicated that hypophysectomized rats present abnormalities of the immune system, including increased thymic atrophy and lymphopenia, a number of studies have focused on the potential immunomodulatory roles of PRL. This hormone exerts its biological activities following binding to specific cell surface PRL receptors (PRLRs). In this report, we have characterized the development and function of the immune system in PRLR-deficient mice. Compared with wild-type control mice, PRLR-/- mice demonstrate no alterations in thymic or splenic cellularity or in the composition of the lymphocyte subsets present in primary (bone marrow and thymus) or secondary (spleen and lymph nodes) lymphoid organs. Lymphocytes from PRLR-/- mice are functional in vitro, as they can proliferate normally to mitogens, cytokines, and allogeneic cells. PRLR-/- splenocytes display normal NK-mediated cytotoxicity to YAC-1 target cells. In vivo studies have revealed that PRLR-/- mice are able to 1) generate normal steady-state Ig levels, 2) mount a normal specific Ig response following immunization with a T-dependent Ag, 3) eliminate injected allogeneic tumor cells, and 4) effectively control Listeria monocytogenes infection. Taken together, these results show that immune system development and function proceed normally in the absence of PRL-mediated signaling and suggest that PRLR pathways are not essential for immunomodulation in vivo.
催乳素（PRL）是腺垂体分泌的主要泌乳激素，在生殖的许多方面发挥着重要作用，从受精到乳腺发育以及母性行为。据报道，PRL在免疫调节中也发挥作用。由于最初的观察表明，垂体切除的大鼠存在免疫系统异常，包括胸腺萎缩加剧和淋巴细胞减少，因此许多研究聚焦于PRL潜在的免疫调节作用。这种激素在与特定的细胞表面PRL受体（PRLRs）结合后发挥其生物学活性。在本报告中，我们对PRLR缺陷小鼠的免疫系统发育和功能进行了表征。与野生型对照小鼠相比，PRLR-/-小鼠的胸腺或脾脏细胞数量以及初级（骨髓和胸腺）或次级（脾脏和淋巴结）淋巴器官中存在的淋巴细胞亚群组成均无改变。PRLR-/-小鼠的淋巴细胞在体外具有功能，因为它们能够正常地对有丝分裂原、细胞因子和异基因细胞进行增殖。PRLR-/-脾细胞对YAC-1靶细胞表现出正常的自然杀伤细胞介导的细胞毒性。体内研究表明，PRLR-/-小鼠能够：1）产生正常的稳态免疫球蛋白水平；2）在用T细胞依赖性抗原免疫后产生正常的特异性免疫球蛋白反应；3）清除注射的异基因肿瘤细胞；4）有效控制单核细胞增生李斯特菌感染。综上所述，这些结果表明，在缺乏PRL介导的信号传导的情况下，免疫系统的发育和功能正常进行，这表明PRLR途径在体内免疫调节中并非必不可少。
