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Enhanced Cell Division Is Required for the Generation of Memory CD4 T Cells to Migrate Into Their Proper Location

CD4 T cell memory is fundamental for long-lasting immunity and effective secondary responses following infection or vaccination. We have previously found that memory CD4 T cells specific for systemic antigens preferentially reside in the bone marrow (BM) and arise from splenic CD49b(+)T-bet(+) CD4 T...

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Detalles Bibliográficos
Autores principales: Sarkander, Jana, Hojyo, Shintaro, Mursell, Mathias, Yamasaki, Yuzuru, Wu, Tsung-Yen, Tumes, Damon J., Miyauchi, Kosuke, Tran, Cam Loan, Zhu, Jinfang, Löhning, Max, Hutloff, Andreas, Mashreghi, Mir-Farzin, Kubo, Masato, Radbruch, Andreas, Tokoyoda, Koji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974474/
https://www.ncbi.nlm.nih.gov/pubmed/32010148
http://dx.doi.org/10.3389/fimmu.2019.03113
Descripción
Sumario:CD4 T cell memory is fundamental for long-lasting immunity and effective secondary responses following infection or vaccination. We have previously found that memory CD4 T cells specific for systemic antigens preferentially reside in the bone marrow (BM) and arise from splenic CD49b(+)T-bet(+) CD4 T cells. However, how BM-homing memory precursors are generated during an immune reaction is unknown. We show here that BM memory precursors are generated via augmented rates of cell division throughout a primary immune response. Treatment with the cytostatic drug cyclophosphamide or blockade of the CD28/B7 co-stimulatory pathway at the beginning of the contraction phase abrogates the generation of BM memory precursors. We determine that, following a critical number of cell divisions, memory precursors downregulate CCR7 and upregulate IL-2Rβ, indicating that loss of CCR7 and gain of IL-2 signal are required for the migration of memory precursors toward the BM.