Terra-Granado Eugênia, Berbert Luiz Ricardo, de Meis Juliana, Nomizo Regina, Martins Vilma Regina, Savino Wilson, Silva-Barbosa Suse Dayse
Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Neuroimmunomodulation. 2007;14(3-4):213-9. doi: 10.1159/000110649. Epub 2007 Dec 5.
The cellular prion protein (PrP(C)) is expressed in the nervous and immune systems. Functionally, PrP(C) has been suggested to participate in neuron survival, neuritogenesis and T lymphocyte activation. Moreover, PrP(C) interaction with laminin influences neuronal adhesion and neurite extension. Nevertheless, so far the physiological role of PrP(C) has not been completely elucidated, particularly in the immune system. The aim of the study was to evaluate the possible participation of PrP(C) in intrathymic T cell development. We evaluated T cell differentiation markers in thymocytes and peripheral lymphocytes, as well as thymocyte death in PrP(C)-null or PrP(C)-overexpressing (Tga20) mice, compared to wild-type controls. In these same animals, we ascertained laminin-driven thymocyte migration. Compared to controls, only marginal differences were found in PrP(C)-null animals. However, Tga20 mice exhibited a severe thymic hypoplasia, with 10-20% lymphocytes compared to wild-type counterparts. In particular, the frequency of CD4+CD8+ cells was largely reduced, and this was accompanied by a dramatic increase in the frequency of CD4-CD8- thymocytes, which could be as high as 60-65% of the whole-cell suspensions. Moreover, Tga20 mice exhibited an increase in thymocyte death, comprising the CD4+CD8+, as well as CD4+ and CD8+ single-positive cells. Additionally, laminin-driven migration was largely impaired in Tga20 mice, in which we also found a significant decrease in total T lymphocytes in the spleen and lymph nodes. Our results show that PrP(C) overexpression alters intrathymic T cell development, a defect that likely has a negative impact in the formation of the T cell peripheral pool.
细胞朊蛋白（PrP(C)）在神经系统和免疫系统中表达。在功能方面，有人提出PrP(C)参与神经元存活、神经突发生和T淋巴细胞活化。此外，PrP(C)与层粘连蛋白的相互作用影响神经元黏附和神经突延伸。然而，到目前为止，PrP(C)的生理作用尚未完全阐明，尤其是在免疫系统中。本研究的目的是评估PrP(C)在胸腺内T细胞发育中的可能作用。我们评估了PrP(C)基因敲除或过表达（Tga20）小鼠与野生型对照相比，胸腺细胞和外周淋巴细胞中的T细胞分化标志物以及胸腺细胞死亡情况。在这些相同的动物中，我们确定了层粘连蛋白驱动的胸腺细胞迁移。与对照相比，在PrP(C)基因敲除动物中仅发现微小差异。然而，Tga20小鼠表现出严重的胸腺发育不全，与野生型对应物相比，淋巴细胞数量减少了10%-20%。特别是，CD4+CD8+细胞的频率大幅降低，同时CD4-CD8-胸腺细胞的频率显著增加，可达全细胞悬液的60%-65%。此外，Tga20小鼠的胸腺细胞死亡增加，包括CD4+CD8+以及CD4+和CD8+单阳性细胞。另外，Tga20小鼠中由层粘连蛋白驱动的迁移受到很大损害，我们还发现其脾脏和淋巴结中的总T淋巴细胞显著减少。我们的结果表明，PrP(C)过表达会改变胸腺内T细胞发育，这种缺陷可能对T细胞外周库的形成产生负面影响。
