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Identification of antigen-presenting cells for memory T helper cells in the recall response

Applicant Dr. Koji Tokoyoda
Subject Area Immunology
Term from 2017 to 2020
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 349354722
 
Final Report Year 2021

Final Report Abstract

Memory Th cells are essential for long-lasting immunity and effective secondary immune responses against previously encountered antigens. However, it remains unknown whether memory Th cells can be reactivated without re-invasion of pathogens or antigens in vivo. A B cell-depleting agent, anti-CD20 antibody, clinically known as Rituximab, was used to investigate the role of B cells in the maintenance and reactivation of memory Th cells. By means of an adoptive transfer model that generates mice harboring antigen-specific memory Th cells, we found that an injection of anti-CD20 but not anti-IgD/M expanded the number of antigen-specific memory Th cells in the spleen. Further analyses showed that the expansion of antigen-specific memory Th cells was dynamically caused by the presentation of antigens remaining in necrotic B cells within 33 days after immunization. Instead of necrotic B cells by anti-CD20, Toll-like receptor 9 agonists, e.g., CpG, together with anti-IgD also induced the expansion of antigen-specific memory Th cells. In addition, we showed that mature B cells are a reservoir of antigens for a certain period of time (33 days, but not 73 days) after immunization. These data suggest that in the case of B cell damages by clinical treatment of anti-CD20, Rituximab and some infections, splenic antigen-specific memory Th cells can be expanded without re-invasion of pathogen. Thus, we alarm that Rituximab for patients with autoimmune diseases may expand auto-reactive memory Th cells and enhance the potential and magnitude of the relapse. In this project, we would identify APCs for memory Th cells in secondary immune response. First, we investigated a role of B cells in secondary immune response by injection of anti-CD20. However, surprisingly, followed by antigen challenge, memory Th cells were expanded. We had doubt on the unexpected result and tried to clarify the reason. The research on identification of APCs for memory Th cells now continues in our lab. However, this switched project found an unexpected phenomenon and clarified a novel cellular and molecular mechanism.

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