CD47 ligation selectively inhibits the development of human naive T cells into Th1 effectors
CD47 ligation selectively inhibits the development of human naive T cells into Th1 effectors
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DOI：
10.4049/jimmunol.165.8.4624
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发表时间：
2000-10-15
影响因子：
4.4
通讯作者：
Sarfati, M
中科院分区：
文献类型：
--
作者：
Avice, MN;Rubio, M;Sarfati, M
CD 47抗原又称整合素相关蛋白，近年来被报道可调节人单核细胞和树突状细胞产生IL-12。本研究表明，CD 47连接的CD 47单克隆抗体在脐带血单核细胞的原代培养物抑制IL-12驱动的Th 1细胞的发展，所揭示的细胞因子分泌概况在再刺激和IFN-γ的生产在单细胞水平。与血小板反应蛋白的CD 47结合位点相对应的CD 47 mAb或合成肽4 N1 K的F（ab '）（2）片段显示相同的活性。CD 47结合不改变IL-12致敏细胞的表型从Th 1到Th 2或影响IL-4诱导的Th 2细胞发育。此外，在原代培养物中，CD 47 mAb抑制IL-12诱导的IL-2产生，但不抑制IL-4诱导的IL-2产生以及IFN-γ产生，这与IL-12 R β 2链表达的降低相关。在引发时包含外源性IL-2校正IL-12 R表达以及抑制Th 1细胞发育。因此，这些数据强调了IL-2在Th 1细胞发育中的作用，并进一步表明同时靶向IL-2和IL-12可能在Th 1自身免疫性疾病中具有一些治疗优势。
The CD47 Ag, also named integrin-associated protein, was recently reported to regulate the production of IL-12 by human monocytes and dendritic cells. The present study shows that CD47 ligation by CD47 mAb in primary cultures of cord blood mononuclear cells inhibits IL-12-driven Th1 cell development, as revealed by the cytokine secretion profile at restimulation and IFN-gamma production at the single-cell level. F(ab')(2) fragments of CD47 mAb or the synthetic peptide 4N1K, corresponding to the CD47 binding site of thrombospondin, display the same activity. CD47 engagement does not change the phenotype of IL-12-primed cells from Th1 to Th2 or affect IL-4-induced Th2 cell development. Moreover, CD47 mAb inhibits IL-12- but not IL-4-induced IL-2 production as well, as IFN-gamma in primary cultures, which was correlated with a decrease of the IL-12R beta 2 chain expression. Inclusion of exogenous IL-2 at priming corrects IL-12R expression as well as the inhibition of Th1 cell development. The data thus underline the role of IL-2 in Th1 cell development and further suggest that targeting IL-2 and IL-12 simultaneously may have some therapeutic advantage in Th1 autoimmune diseases.