B cell depletion impairs vaccination-induced CD8+ T cell responses in a type I interferon-dependent manner.
Ann Rheum Dis
; 80(12): 1537-1544, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34226189
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
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Vacinas contra Influenza
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Linfócitos B
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Interferon Tipo I
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Linfócitos T CD8-Positivos
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Antirreumáticos
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Rituximab
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Imunogenicidade da Vacina
Tipo de estudo:
Observational_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Ann Rheum Dis
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha