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Dampening of CD8+ T Cell Response by B Cell Depletion Therapy in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Abstract : Objective. To compare the effects of rituximab (RTX) and conventional immunosuppressants (CIs) on CD4+ T cells, Treg cells, and CD8+ T cells in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods. A thorough immunophenotype analysis of CD4+, Treg, and CD8+ cells from 51 patients with AAV was performed. The production of cytokines and chemokines by CD8+ T cells stimulated in vitro was assessed using a multiplex immunoassay. The impact of AAV B cells on CD8+ T cell response was assessed using autologous and heterologous cocultures. Results. CD4+ and Treg cell subsets were comparable among RTX-treated and CI-treated patients. In contrast, within the CD8+ T cell compartment, RTX, but not CIS, reduced CD45RA+CCR7-(TEMRA) cell frequency (from a median of 39% before RTX treatment to 10% after RTX treatment [P < 0.01]) and efficiently dampened cytokine/chemok-ine 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]). CD8+ 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-CD8+ T cell cross-talk reduced CD8+ T cell cytokine production, mirroring the reduced CD8+ response observed ex vivo after RTX treatment. Conclusion. The disruption of a pathogenic B cell/CD8+ T cell axis may contribute to the efficacy of RTX in AAV. Further studies are needed to determine the value of CD8+ T cell immunomonitoring in B cell-targeted therapies.
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Submitted on : Friday, June 14, 2019 - 1:57:22 PM
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Antoine Néel, Marie Bucchia, Mélanie Néel, Gaëlle Tilly, Aurélie Caristan, et al.. Dampening of CD8+ T Cell Response by B Cell Depletion Therapy in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis. Arthritis & rheumatology, Wiley, 2019, 71 (4), pp.641-650. ⟨10.1002/art.40766⟩. ⟨inserm-02156485⟩



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