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Maintenance of T helper cell memory

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If you have a question about this talk, please contact Prof. Jim Kaufman.

Host: Nick Holmes (nh106@cam.ac.uk)

A biologist by education, Andreas Radbruch has focussed his scientific work since 1976 on the immune system, and the way it provides immunity or participates in immunopathology. In particular, his work aims at a molecular understanding of the quantitative and qualitative control of immune reactions and the immunological memory. Andreas Radbruch was first to show that switch recombination had occurred physiologically in switched memory B lymphocytes and antibody secreting plasma cells. He could paradigmatically show for the murine IgG1 gene that a region that is addressed by signals from the interleukin-4 receptor and promotes transcription of the corresponding gene segments, is essential for switch recombination, and links it to RNA processing.

Initially with the aim to understand class which regulation, the group of A. Radbruch has focussed then on the question of how expression of those cytokines is controlled in T lymphocytes, in particular the cytokine Interleukin-4, a central regulator of humoral immunity and allergy. In recent and ongoing work, his group analyses the molecular basis of this “cytokine memory”, changes in transcription factor setup and epigenetic modification of the cytokine genes in effector and memory T lymphocytes. This work has a major impact on recent concepts on immunological memory and chronic immunopathology. At that time, the group of Andreas Radbruch has also developed high-gradient magnetic cell sorting (MACS).

More recently, the group of Andreas Radbruch has addressed the biology of plasma cells which confer the humoral immunological memory, i.e. the protection provided by serum antibodies specific for antigens encountered in the past. The new concept of long-lived (memory plasma cells as the basis of humoral immunity has drastic consequences for the development of vaccination strategies and for the understanding and treatment of antibody-mediated immunopathology in allergy and autoimmunity. And it appears that those principles of organisation of plasma cell memory also apply to the organisation of T helper cell memory. The molecular analysis of immunological memory in immunity and immunopathology of the Radbruch group now aims at defining, from a basic understanding of their biology, strategies for the selective depletion of the “pathogenic” memory driving chronic inflammatory diseases.

This talk is part of the Immunology in Pathology series.

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