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B cell depletion impairs vaccination-induced CD8 T cell responses in a type I interferon-dependent manner.
Graalmann, Theresa Borst, Katharina Manchanda, Himanshu Vaas, Lea Bruhn, Matthias Graalmann, Lukas Koster, Mario Verboom, Murielle Hallensleben, Michael Guzmán, Carlos Alberto
Graalmann, Theresa
Borst, Katharina
Manchanda, Himanshu
Vaas, Lea
Bruhn, Matthias
Graalmann, Lukas
Koster, Mario
Verboom, Murielle
Hallensleben, Michael
Guzmán, Carlos Alberto
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2021-07-05
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Abstract
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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Ann Rheum Dis. 2021 Jul 5:annrheumdis-2021-220435. doi: 10.1136/annrheumdis-2021-220435. Epub ahead of print.
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en
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1468-2060
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Attribution 4.0 International