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Proceedings of the National Academy of Sciences of the United States of America v.115 no.6, 2018년, pp.1334 - 1339   SCI SCIE
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Nonfollicular reactivation of bone marrow resident memory CD4 T cells in immune clusters of the bone marrow

Siracusa, Francesco (Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, 10117 Berlin, Germany ) ; McGrath, Mairi A. (Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, 10117 Berlin, Germany ) ; Maschmeyer, Patrick (Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, 10117 Berlin, Germany ) ; Bardua, Markus (Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, 10117 Berlin, Germany ) ; Lehmann, Katrin (Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, 10117 Berlin, Germany ) ; Heinz, Gitta (Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, 10117 Berlin, Germany ) ; Durek, Pawel (Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, 10117 Berlin, Germany ) ; Heinrich, Frederik F. (Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, 10117 Berlin, Germany ) ; Mashreghi, Mir-Farzin (Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, 10117 Berlin, Germany ) ; Chang, Hyun-Dong (Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, 10117 Berlin, Germany ) ; Tokoyoda, Koji (Osteoimmunology, DRFZ Berlin, 10117 Berlin, Germany ) ; Radbruch, Andreas (Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) ) ;
  • 초록  

    Significance The bone marrow (BM) harbors critical components of the adaptive immune system able to provide long-lasting protection against pathogens. Among those, CD4 memory T cells are potent helpers of immune reactions in secondary lymphoid organs. Here we analyze their reactivation in the BM in secondary immune reactions. The CD4 memory T cells form clusters with antigen-presenting cells and proliferate vigorously. Although these clusters contain many B lymphocytes, their formation is not dependent on them and no germinal centers develop. Rather, antigen-specific CD4 memory T cells are significantly amplified and, after termination of the immune reaction, they remain in the BM as resting cells. The BM thus provides a dynamic reservoir of CD4 memory T cells, adapting quantitatively to antigenic challenges. The bone marrow maintains memory CD4 T cells, which provide memory to systemic antigens. Here we demonstrate that memory CD4 T cells are reactivated by antigen in the bone marrow. In a secondary immune response, antigen-specific T cells of the bone marrow mobilize and aggregate in immune clusters together with MHC class II-expressing cells, mostly B lymphocytes. They proliferate vigorously and express effector cytokines, but they do not develop into follicular T-helper cells. Neither do the B lymphocytes develop into germinal center B cells in the bone marrow. Within 10 days, the immune clusters disappear again. Within 30 days, the expanded antigen-specific memory CD4 T cells return to memory niches and are maintained again individually as resting cells. Thus, in secondary immune responses in the bone marrow T-cell memory is amplified, while in germinal center reactions of secondary lymphoid organs humoral memory is adapted by affinity maturation.


  • 주제어

    bone marrow .   tissue-resident CD4 memory T cells .   reactivation .   immune clusters .   secondary immune reaction.  

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