Tamura Chizuru, Nakazawa Masatoshi, Kasahara Masaki, Hotta Chie, Yoshinari Masahiro, Sato Fumitaka, Minami Mutsuhiko
Department of Immunology, Yokohama City University School of Medicine, Yokohama, Japan.
Autoimmunity. 2006 Sep;39(6):445-53. doi: 10.1080/08916930600833390.
Alymphoplasia (aly/aly) mice are from a naturally occurring strain with a mutation in nuclear factor-kappa B inducing kinase (NIK). The NIK mutation causes disruption of the architecture of the thymus and spleen and aly/aly mice show decreased numbers of CD25+CD4+T cells in the spleen. For the expansion of CD25+CD4+T cells, interactions between dendritic cells (DCs) and CD25+CD4+ regulatory T cells are necessary. We investigated the ability of DCs to induce expansion of CD25+CD4+T cells. We found that DCs are reduced in the spleen of aly/aly mice, and showed low expressions of CD80, CD86 and MHC class II molecules on the surface. DCs from aly/aly mice showed decreased ability to present ovalbumin (OVA) to T cells from OVA specific TCR transgenic mice, and a decreased ability for alloantigen presentation. Further, DCs showed a decreased ability to induce expansion of CD25+CD4+T cells in vitro. Our results suggested that the impairment of DCs in aly/aly mice is responsible, at least in part, for the decreased numbers of CD25+CD4+T cells in the periphery of aly/aly mice.
无淋巴细胞血症（aly/aly）小鼠源自一种自然发生的品系，其核因子κB诱导激酶（NIK）发生了突变。NIK突变导致胸腺和脾脏结构破坏，aly/aly小鼠脾脏中CD25⁺CD4⁺T细胞数量减少。对于CD25⁺CD4⁺T细胞的扩增，树突状细胞（DC）与CD25⁺CD4⁺调节性T细胞之间的相互作用是必要的。我们研究了DC诱导CD25⁺CD4⁺T细胞扩增的能力。我们发现aly/aly小鼠脾脏中的DC数量减少，且其表面CD80、CD86和MHC II类分子表达较低。aly/aly小鼠的DC向OVA特异性TCR转基因小鼠的T细胞呈递卵清蛋白（OVA）的能力下降，同种抗原呈递能力也下降。此外，DC在体外诱导CD25⁺CD4⁺T细胞扩增的能力下降。我们的结果表明，aly/aly小鼠中DC的损伤至少部分导致了aly/aly小鼠外周血中CD25⁺CD4⁺T细胞数量的减少。
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