Enhanced cell division is required for the generation of memory CD4 T cells to migrate into their proper location
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Date
2020
Authors
Sarkander, J.
Hojyo, S.
Mursell, M.
Yamasaki, Y.
Wu, T.Y.
Tumes, D.J.
Miyauchi, K.
Tran, C.L.
Zhu, J.
Löhning, M.
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Journal article
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Frontiers in Immunology, 2020; 10(3113):1-12
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Abstract
CD4 T cell memory is fundamental for long-lasting immunity and effective secondary responses following infection or vaccination. We have previously found that memoryCD4 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 down regulate CCR7 and upregulate IL-2Rb, indicating that loss of CCR7 and gain of IL-2 signal are required for the migration of memory precursors toward the BM.
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Data source: Supplementary material, https://www.frontiersin.org/articles/10.3389/fimmu.2019.03113/full#supplementary-material
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Copyright 2020 Sarkander, Hojyo, Mursell, Yamasaki, Wu, Tumes, Miyauchi,Tran, Zhu, Löhning, Hutloff, Mashreghi, Kubo, Radbruch and Tokoyoda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted,provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. (https://creativecommons.org/licenses/by/4.0/)