Splenic TFH expansion participates in B-cell differentiation and antiplatelet-antibody production during immune thrombocytopenia

被引:71
作者
Audia, Sylvain [1 ,2 ,3 ]
Rossato, Marzia [1 ]
Santegoets, Kim [1 ]
Spijkers, Sanne [1 ]
Wichers, Catharina [1 ]
Bekker, Cornelis [1 ]
Bloem, Andries [1 ]
Boon, Louis [4 ]
Flinsenberg, Thijs [1 ]
Compeer, Ewoud [1 ]
van den Broek, Theo [1 ]
Facy, Olivier [5 ]
Ortega-Deballon, Pablo [5 ]
Berthier, Sabine [3 ]
Leguy-Seguin, Vanessa [3 ]
Martin, Laurent [2 ,6 ]
Ciudad, Marion [2 ]
Samson, Maxime [2 ]
Trad, Malika [2 ]
Lorcerie, Bernard [3 ]
Janikashvili, Nona [2 ]
Saas, Philippe [2 ]
Bonnotte, Bernard [2 ,3 ]
Radstake, Timothy R. D. J. [1 ]
机构
[1] Univ Med Ctr, Lab Translat Immunol, Utrecht, Netherlands
[2] Univ Bourgogne Franche Comte, Ctr Rech INSERM 1098, Federat Hosp Univ Integrated Ctr Res Inflammatory, Bourgogne, France
[3] Univ Hosp, Dept Internal Med & Clin Immunol, Competence Ctr Autoimmune Cytopenia, Dijon, France
[4] Bioceros, Utrecht, Netherlands
[5] Univ Hosp, Dept Surg, Dijon, France
[6] Univ Hosp, Dept Pathol, Dijon, France
关键词
HELPER T-CELLS; ANTI-CD154; MONOCLONAL-ANTIBODY; GERMINAL-CENTERS; IL-21; SPLEEN; SUBSET; AUTOANTIBODIES; ACTIVATION; PHENOTYPE; RITUXIMAB;
D O I
10.1182/blood-2014-03-563445
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Antiplatelet-antibody-producing B cells play a key role immune thrombocytopenia (ITP) pathogenesis; however, little is known about T-cell dysregulations that support B-cell differentiation. During the past decade, T follicular helper cells (TFHs) have been characterized as the main T-cell subset within secondary lymphoid organs that promotes B-cell differentiation leading to antibody class-switch recombination and secretion. Herein, we characterized TFHs within the spleen of 8 controls and 13 ITP patients. We show that human splenic TFHs are the main producers of interleukin (IL)-21, express CD40 ligand(CD154), and are located within the germinal center of secondary follicles. Compared with controls, splenic TFH frequency is higher in ITP patients and correlates with germinal center and plasma cell percentages that are also increased. In vitro, IL-21 stimulation combined with an anti-CD40 agonist antibody led to the differentiation of splenic B cells into plasma cells and to the secretion of antiplatelet antibodies in ITP patients. Overall, these results point out the involvement of TFH in ITP pathophysiology and the potential interest of IL-21 and CD40 as therapeutic targets in ITP.
引用
收藏
页码:2858 / 2866
页数:9
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