Immunology-oncology Section, Maisonneuve-Rosemont Hospital, Montreal, Quebec, H1T 2M4 Canada.
J Autoimmun. 2010 Aug;35(1):23-32. doi: 10.1016/j.jaut.2010.01.002. Epub 2010 Feb 6.
CD47 and signal regulatory protein (SIRP) interactions have been proposed to take part in autoimmune disease susceptibility. Importantly, a recent genome-wide association study for type 1 diabetes susceptibility highlighted the association of the 20p13 region comprising the SIRP cluster, where some of the SIRP proteins encode functional ligands to CD47. Using a TCR transgenic mouse model at the brink of autoimmune disease, we demonstrate that CD47-deficiency is sufficient to break the immune tolerance and provoke the onset of autoimmune diabetes. Interestingly, CD47-deficient mice show a severe reduction in the number of mature CD4(-)CD8(-) T cells, and passive transfer of these CD4(-)CD8(-) T cells is sufficient to restore immune tolerance and prevent diabetes progression. Together, these findings constitute an in vivo demonstration that CD47 is involved in diabetes susceptibility and controls the homeostatic regulation of CD4(-)CD8(-) T cells.
CD47 和信号调节蛋白（SIRP）的相互作用被认为参与了自身免疫性疾病的易感性。重要的是，最近一项针对 1 型糖尿病易感性的全基因组关联研究强调了包含 SIRP 簇的 20p13 区域的关联，其中一些 SIRP 蛋白编码 CD47 的功能配体。我们使用一种处于自身免疫性疾病边缘的 TCR 转基因小鼠模型，证明 CD47 缺陷足以打破免疫耐受并引发自身免疫性糖尿病的发生。有趣的是，CD47 缺陷小鼠表现出成熟 CD4(-)CD8(-)T 细胞数量的严重减少，并且这些 CD4(-)CD8(-)T 细胞的被动转移足以恢复免疫耐受并防止糖尿病进展。这些发现共同构成了体内证明 CD47 参与糖尿病易感性并控制 CD4(-)CD8(-)T 细胞的稳态调节的证据。
