Memory T helper (Th) lymphocytes are critical for the generation, maintenance and reactivation of other memory cells and play a crucial role in maintaining and provoking protective memory to infectious pathogens and pathogenic memory to autoantigens. Despite their central role, the generation, maintenance and reactivation of pathogen-specific and auto-reactive memory Th cells in the body still remain unclear.
Recently, we have found and further described the microenvironment ‘niches’ for survival of pathogen-specific memory plasma cells and memory Th cells in the bone marrow (BM). Memory plasma cells adhere to CXCL12-expressing stromal cells and memory Th cells are maintained on IL-7-expressing stromal cells. Although it had been commonly thought that memory Th cells are circulating and maintained antigen-dependently, we exhibited that pathogen-specific memory Th cells are not circulating and instead reside and rest in the BM antigen-independently. In 2012 and 2013, we have reported that CD69 and CD49b (integrin alpha2) are required as homing receptors for the generation and maintenance of pathogen-specific memory Th cells in the BM.
We have so far shown how pathogen-specific memory Th cells are generated and maintained in the body. There is still much to discover about the reactivation of pathogen-specific memory Th cells, i.e. memory response, and also about the generation and maintenance of auto-reactive memory Th cells. In the case of memory response, the complex and still widely unknown collaboration by BM memory Th cells and splenic memory B cells should be clarified. We currently study the cellular and molecular mechanisms of humoral memory response in the body, focusing on memory Th cells. For auto-reactive memory Th cells, comparing them with pathogen-specific memory cells, we aim at understanding how auto-reactive memory Th cells are generated and maintained in the body.
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Koji Tokoyoda, PhD
Shintaro Hojyo, PhD
Prof. Dr. Max Löhning, DRFZ, Experimental Immunology, Berlin, Germany
Prof. Dr. Toshinori Nakayama, Immunology, Chiba University, Chiba, Japan
Prof. Dr. Andreas Radbruch, DRFZ, Cell Biology, Berlin, Germany
Prof. Dr. Tomoko Yamamoto, Dr. Akiko Takaya, Microbiology, Chiba University, Chiba, Japan