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Nonfollicular reactivation of bone marrow resident memory CD4 T cells in immune clusters of the bone marrow.


ABSTRACT: 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.

SUBMITTER: Siracusa F 

PROVIDER: S-EPMC5819416 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Nonfollicular reactivation of bone marrow resident memory CD4 T cells in immune clusters of the bone marrow.

Siracusa Francesco F   McGrath Mairi A MA   Maschmeyer Patrick P   Bardua Markus M   Lehmann Katrin K   Heinz Gitta G   Durek Pawel P   Heinrich Frederik F FF   Mashreghi Mir-Farzin MF   Chang Hyun-Dong HD   Tokoyoda Koji K   Radbruch Andreas A  

Proceedings of the National Academy of Sciences of the United States of America 20180122 6


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 ly  ...[more]

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