Bruce Danny, Whitcomb James P, August Avery, McDowell Mary Ann, Cantorna Margherita T
Department of Veterinary and Biomedical Science, Center for Immunology and Infectious Disease, Pennsylvania State University, University Park, PA 16802, USA.
Int Immunol. 2009 Feb;21(2):113-22. doi: 10.1093/intimm/dxn129. Epub 2008 Dec 15.
1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and the vitamin D receptor (VDR) are important regulators of autoimmunity. The effect of the VDR on the ability of mice to fight a primary or secondary infection has not been determined. Young and old VDR knockout (KO) mice were able to clear both primary and secondary infections with Listeria monocytogenes. However, the kinetics of clearance was somewhat delayed in the absence of the VDR. Memory T cell development was not different in young VDR KO and wild-type (WT) mice; however, old VDR KO mice had significantly less memory T cells than their WT counterparts but still mounted an adequate immune response as determined by the complete clearance of L. monocytogenes. Although the primary and secondary immune responses were largely intact in the VDR KO mice, the old VDR KO mice had increased cytokines and antibody responses compared with the old WT mice. In particular, old VDR KO mice had elevated antigen non-specific antibodies; however, these magnified immune responses did not correspond to more effective Listeria clearance. The increased antibody and cytokine responses in the old VDR KO mice are consistent with the increased susceptibility of these mice to autoimmunity.
1,25 - 二羟基维生素D(3)[1,25(OH)₂D₃]和维生素D受体(VDR)是自身免疫的重要调节因子。VDR对小鼠抵抗原发性或继发性感染能力的影响尚未确定。年轻和年老的VDR基因敲除(KO)小鼠都能够清除单核细胞增生李斯特菌的原发性和继发性感染。然而,在没有VDR的情况下,清除动力学有所延迟。年轻的VDR KO小鼠和野生型(WT)小鼠的记忆T细胞发育没有差异;然而,年老的VDR KO小鼠的记忆T细胞明显少于其WT对应物,但仍能通过单核细胞增生李斯特菌的完全清除产生足够的免疫反应。尽管VDR KO小鼠的原发性和继发性免疫反应基本完整,但与年老的WT小鼠相比,年老的VDR KO小鼠的细胞因子和抗体反应有所增加。特别是,年老的VDR KO小鼠的抗原非特异性抗体升高;然而,这些放大的免疫反应并不对应于更有效的李斯特菌清除。年老的VDR KO小鼠中抗体和细胞因子反应的增加与这些小鼠对自身免疫易感性的增加一致。