State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, People's Republic of China.
J Clin Immunol. 2011 Aug;31(4):632-42. doi: 10.1007/s10875-011-9539-1. Epub 2011 May 4.
CD70 and CD11a are co-stimulatory molecules that are important for the immune functions of T, B lymphocytes. Over-expressions of CD70 or CD11a cause T cell to be autoreactive.
The purpose of this study was to explore the effect of CD70 and CD11a in immune thrombocytopenia (ITP).
CD70 and CD11a mRNAs and protein expressions in CD4(+) T cells from ITP patients were measured respectively by real-time quantitative-PCR (RT-PCR) and flow cytometry. The apoptosis of T cells, B cells, and platelets in the PBMCs were analyzed by flow cytometry, and secretion of IL-4, IFN-γ, as well as IgG in the reaction supernatant were detected by ELISA. In order to investigate the effects of CD70 and CD11a over-expression on pathogenesis of ITP, anti-CD70, and anti-CD11a mAbs were used to block the signaling pathways.
CD70 and CD11a mRNAs and protein expressions in CD4(+) T cells from ITP patients were significantly higher than healthy controls. In vitro co-culturing of PBMCs with anti-CD70 or anti-CD11a, the apoptosis of T, B lymphocytes were significantly increased but apoptosis of platelets were reduced. Anti-CD11a and anti-CD70 both significantly suppressed the secretion of IFN-γ, while anti-CD11a significantly promoted the secretion of IL-4. There was no significant difference in the healthy group.
CD70 and CD11a facilitate the survival of T, B lymphocytes and indirectly enhance the destruction of platelets in ITP. Blockade of CD70 or CD11a are promising therapeutic approaches for ITP.
CD70 和 CD11a 是共刺激分子，对 T、B 淋巴细胞的免疫功能很重要。CD70 或 CD11a 的过度表达可导致 T 细胞自身反应性。
本研究旨在探讨 CD70 和 CD11a 在免疫性血小板减少症（ITP）中的作用。
采用实时定量 PCR（RT-PCR）和流式细胞术分别检测 ITP 患者 CD4+T 细胞中 CD70 和 CD11a mRNA 和蛋白的表达。用流式细胞术分析 PBMC 中 T 细胞、B 细胞和血小板的凋亡情况，用 ELISA 检测反应上清液中 IL-4、IFN-γ和 IgG 的分泌。为了探讨 CD70 和 CD11a 过表达对 ITP 发病机制的影响，用抗 CD70 和抗 CD11a mAb 阻断信号通路。
ITP 患者 CD4+T 细胞中 CD70 和 CD11a mRNA 和蛋白的表达明显高于健康对照组。体外共培养 PBMCs 与抗 CD70 或抗 CD11a，T、B 淋巴细胞的凋亡明显增加，但血小板的凋亡减少。抗 CD11a 和抗 CD70 均明显抑制 IFN-γ的分泌，而抗 CD11a 明显促进 IL-4 的分泌。在健康组中无显著差异。
CD70 和 CD11a 促进 T、B 淋巴细胞的存活，并间接增强 ITP 中血小板的破坏。阻断 CD70 或 CD11a 可能是 ITP 的一种有前途的治疗方法。
