Li Ma1, Zeping Zhou, Hairong Jia, Hu Zhou, Aiping Qi, Huiyuan Li, Hongmei Wang, Lei Zhang, Renchi Yang. 1. 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.
Abstract
INTRODUCTION: 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. OBJECTIVES: The purpose of this study was to explore the effect of CD70 and CD11a in immune thrombocytopenia (ITP). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
INTRODUCTION: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. OBJECTIVES: The purpose of this study was to explore the effect of CD70 and CD11a in immune thrombocytopenia (ITP). METHODS: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. RESULTS: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. CONCLUSIONS: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.
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