Preferential splenic CD8+ T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia
Preferential splenic CD8+ T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia
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DOI：
10.1182/blood-2013-03-491415
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发表时间：
2013-10-03
期刊：
影响因子：
20.3
通讯作者：
Bonnotte, Bernard
中科院分区：
文献类型：
--
作者：
Audia, Sylvain;Samson, Maxime;Bonnotte, Bernard
B细胞在免疫性血小板减少症（ITP）中的致病作用证明了抗CD20抗体如利妥昔单抗（RTX）的治疗用途是合理的。然而，60%的ITP患者对RTX没有反应。为了解释RTX失败的机制，并且因为脾脏在ITP发病机制中起着公认的作用，将来自对RTX治疗无应答的ITP患者的12个脾脏与来自未经RTX治疗的ITP患者和9个对照的11个脾脏进行比较。我们在此证明，在RTX无应答ITP患者中，优先Th1和Tc1 T淋巴细胞极化发生，与脾脏效应记忆CD8（+）T细胞频率增加相关。此外，在RTX无应答患者组中，CD8（+）T细胞库显示出有限的模式。在血液中，RTX治疗前后的CD8（+）T细胞表型在应答者或无应答者中没有改变。总而言之，这些结果首次证明了对RTX无反应的ITP患者脾脏CD8（+）T细胞的活化，并表明它们参与了这些患者的血小板破坏。
The pathogenic role of B cells in immune thrombocytopenia (ITP) has justified the therapeutic use of anti-CD20 antibodies such as rituximab (RTX). However, 60% of ITP patients do not respond to RTX. To decipher the mechanisms implicated in the failure of RTX, and because the spleen plays a well-recognized role in ITP pathogenesis, 12 spleens from ITP patients who had been nonresponders to RTX therapy were compared with 11 spleens from RTX-untreated ITP patients and 9 controls. We here demonstrate that in RTX-nonresponder ITP patients, preferential Th1 and Tc1 T lymphocyte polarizations occur, associated with an increase in splenic effector memory CD8(+) T-cell frequency. Moreover, in the RTX-nonresponder patient group, the CD8(+) T-cell repertoire displays a restricted pattern. In the blood, the phenotype of CD8(+) T cells before and after RTX treatment is not modified in responders or nonresponders. Altogether, these results demonstrate for the first time an activation of splenic CD8(+) T cells in ITP patients who did not respond to RTX and suggest their involvement in platelet destruction in these patients.