B cell depletion impairs vaccination-induced CD8+ T cell responses in a type I interferon-dependent manner

• Published in: Annals of the rheumatic diseases Vol. 80; no. 12; pp. 1537 - 1544
• Main Authors: Graalmann, Theresa, Borst, Katharina, Manchanda, Himanshu, Vaas, Lea, Bruhn, Matthias, Graalmann, Lukas, Koster, Mario, Verboom, Murielle, Hallensleben, Michael, Guzmán, Carlos Alberto, Sutter, Gerd, Schmidt, Reinhold E, Witte, Torsten, Kalinke, Ulrich
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and European League Against Rheumatism 01.12.2021; Elsevier Limited; BMJ Publishing Group
• Subjects: Animals; Antibodies; Antirheumatic Agents - adverse effects; Arthritis; Arthritis, Rheumatoid - drug therapy; Autoimmune diseases; B-Lymphocytes; B-Lymphocytes - immunology; Case-Control Studies; CD20 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Chemokines; COVID-19; Cytokines; Cytokines - immunology; Cytotoxicity; Histocompatibility Antigens Class I - immunology; Humans; Immunogenicity, Vaccine - immunology; Immunotherapy; Infections; Influenza; Influenza Vaccines - immunology; Influenza Vaccines - therapeutic use; Influenza, Human - prevention & control; Interferon; Interferon Type I - immunology; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma; Major histocompatibility complex; Mice; Monoclonal antibodies; Orthomyxoviridae - immunology; Orthomyxoviridae Infections - immunology; Pandemics; Patients; Rheumatoid; Rheumatoid Arthritis; Rituximab; Rituximab - adverse effects; Severe acute respiratory syndrome coronavirus 2; T-Lymphocyte subsets; Targeted cancer therapy; Vaccination; Vaccines; Vaccinia - immunology; Vaccinia virus - immunology; Viruses; Ankara Turkey; Turkey; Rheumatoid; B-Lymphocytes; Rituximab; T-Lymphocyte subsets; Arthritis; Vaccination
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2021-220435

ObjectivesThe 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.MethodsCD8+ T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens.ResultsRituximab-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.ConclusionsDepending 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.