title: Preferential splenic CD8(+) T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia.
abstract: 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.
authors: Centre de Recherche, National de la Santé et de la Recherche Médicale 1098, University of Franche-Comté, Besançon, France;
authors: Sylvain
authors: S
authors: Audia
authors: Maxime
authors: M
authors: Samson
authors: Matthieu
authors: M
authors: Mahévas
authors: Christophe
authors: C
authors: Ferrand
authors: Malika
authors: M
authors: Trad
authors: Marion
authors: M
authors: Ciudad
authors: Alexandrine
authors: A
authors: Gautheron
authors: Famky
authors: F
authors: Seaphanh
authors: Vanessa
authors: V
authors: Leguy
authors: Sabine
authors: S
authors: Berthier
authors: Bruno
authors: B
authors: Salles
authors: Laurent
authors: L
authors: Martin
authors: Bernard
authors: B
authors: Lorcerie
authors: Pablo
authors: P
authors: Ortega-Deballon
authors: Olivier
authors: O
authors: Facy
authors: Denis
authors: D
authors: Caillot
authors: Agnès
authors: A
authors: Soudry-Faure
authors: Marc
authors: M
authors: Michel
authors: Bertrand
authors: B
authors: Godeau
authors: Nicolas
authors: N
authors: Larmonier
authors: Philippe
authors: P
authors: Saas
authors: Nona
authors: N
authors: Janikashvili
authors: Bernard
authors: B
authors: Bonnotte
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004351:Drug Resistance / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D000069283:Rituximab; D013154:Spleen / Q000276:immunology; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab