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Dampening of CD8+ T Cell Response by B Cell Depletion Therapy in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Author(s) -
Néel Antoine,
Bucchia Marie,
Néel Mélanie,
Tilly Gaelle,
Caristan Aurélie,
Yap Michele,
Rimbert Marie,
Bruneau Sarah,
Cadoux Marion,
Agard Christian,
Hourmant Maryvonne,
Godmer Pascal,
Brouard Sophie,
Bressollette Céline,
Hamidou Mohamed,
Josien Regis,
Fakhouri Fadi,
Degauque Nicolas
Publication year - 2019
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40766
Subject(s) - cd8 , cytotoxic t cell , immunology , t cell , proinflammatory cytokine , chemokine , cytokine , medicine , microbiology and biotechnology , biology , chemistry , inflammation , immune system , in vitro , biochemistry
Objective To compare the effects of rituximab ( RTX ) and conventional immunosuppressants ( CIs ) on CD 4+ T cells, Treg cells, and CD 8+ T cells in antineutrophil cytoplasmic antibody–associated vasculitis ( AAV ). Methods A thorough immunophenotype analysis of CD 4+, Treg, and CD 8+ cells from 51 patients with AAV was performed. The production of cytokines and chemokines by CD 8+ T cells stimulated in vitro was assessed using a multiplex immunoassay. The impact of AAV B cells on CD 8+ T cell response was assessed using autologous and heterologous cocultures. Results CD 4+ and Treg cell subsets were comparable among RTX ‐treated and CI ‐treated patients. In contrast, within the CD 8+ T cell compartment, RTX , but not CIS , reduced CD 45 RA + CCR 7– ( TEMRA ) cell frequency (from a median of 39% before RTX treatment to 10% after RTX treatment [ P < 0.01]) and efficiently dampened cytokine/chemokine production (e.g., the median macrophage inflammatory protein 1α level was 815 pg/ml in patients treated with RTX versus 985 pg/ml in patients treated with CIs versus 970 pg/ml in those with active untreated AAV [ P < 0.01]). CD 8+ T cell subsets cocultured with autologous B cells produced more proinflammatory cytokines in AAV patients than in controls (e.g., for tumor necrosis factor–producing effector memory CD8+ T cells: 14% in AAV patients versus 9.2% in controls [ P < 0.05]). In vitro disruption of AAV B cell– CD 8+ T cell cross‐talk reduced CD 8+ T cell cytokine production, mirroring the reduced CD 8+ response observed ex vivo after RTX treatment. Conclusion The disruption of a pathogenic B cell/ CD 8+ T cell axis may contribute to the efficacy of RTX in AAV . Further studies are needed to determine the value of CD 8+ T cell immunomonitoring in B cell–targeted therapies.