期刊
ANNALS OF THE RHEUMATIC DISEASES
卷 80, 期 12, 页码 1537-1544出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/annrheumdis-2021-220435
关键词
Rituximab; Arthritis; Rheumatoid; Vaccination; B-Lymphocytes; T-Lymphocyte subsets
类别
资金
- German Centre for Infection Research [DZIF TTU 07.806_00]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy [EXC 2155, 39087428]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [158989968 -SFB 900]
- German Federal Ministry of Education and Research (BMBF) [01GM1910E]
Rituximab-treated patients and B cell-deficient mice showed reduced expansion of virus-specific CD8(+) T cells after vaccination/infection with different vaccines/pathogens, indicating that B cells can modulate CD8(+) T cell responses. The choice of vaccines for B cell-depleted patients needs to be re-evaluated to effectively induce protective CD8(+) T cell responses.
Objectives The monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses. Methods CD8(+) T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens. Results Rituximab-treated RA patients vaccinated with Influvac showed reduced expansion of influenza-specific CD8(+) T cells when compared with healthy controls. Moreover, B cell-deficient JHT mice infected with mouse-adapted Influenza or modified vaccinia virus Ankara showed less vigorous expansion of virus-specific CD8(+) T cells than wild type mice. Of note, JHT mice do not have an intrinsic impairment of CD8(+) T cell expansion, since infection with vaccinia virus induced similar T cell expansion in JHT and wild type mice. Direct type I interferon receptor signalling of B cells was necessary to induce several chemokines in B cells and to support T cell help by enhancing the expression of MHC-I. Conclusions Depending on the stimulus, B cells can modulate CD8(+) T cell responses. Thus, B cell depletion causes a deficiency of de novo antibody responses and affects the efficacy of cellular response including cytotoxic T cells. The choice of the appropriate vaccine to vaccinate B cell-depleted patients has to be re-evaluated in order to efficiently induce protective CD8(+) T cell responses.
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