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 cel...
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doaj-f7e58968267c4ca28fd3c9813a104a1c2020-11-25T00:12:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-01-011010.3389/fimmu.2019.03113498935Enhanced Cell Division Is Required for the Generation of Memory CD4 T Cells to Migrate Into Their Proper LocationJana Sarkander0Shintaro Hojyo1Mathias Mursell2Yuzuru Yamasaki3Tsung-Yen Wu4Damon J. Tumes5Kosuke Miyauchi6Cam Loan Tran7Jinfang Zhu8Max Löhning9Max Löhning10Andreas Hutloff11Mir-Farzin Mashreghi12Masato Kubo13Masato Kubo14Andreas Radbruch15Koji Tokoyoda16Deutsches Rheuma-Forschungszentrum Berlin, Leibniz Institute, Berlin, GermanyDeutsches Rheuma-Forschungszentrum Berlin, Leibniz Institute, Berlin, GermanyDeutsches Rheuma-Forschungszentrum Berlin, Leibniz Institute, Berlin, GermanyDeutsches Rheuma-Forschungszentrum Berlin, Leibniz Institute, Berlin, GermanyDeutsches Rheuma-Forschungszentrum Berlin, Leibniz Institute, Berlin, GermanyCentre for Cancer Biology, SA Pathology and The University of South Australia, Adelaide, SA, AustraliaLaboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanDeutsches Rheuma-Forschungszentrum Berlin, Leibniz Institute, Berlin, GermanyLaboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesDeutsches Rheuma-Forschungszentrum Berlin, Leibniz Institute, Berlin, GermanyExperimental Immunology and Osteoarthritis Research, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, GermanyDeutsches Rheuma-Forschungszentrum Berlin, Leibniz Institute, Berlin, GermanyDeutsches Rheuma-Forschungszentrum Berlin, Leibniz Institute, Berlin, GermanyLaboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanDivision of Molecular Pathology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, JapanDeutsches Rheuma-Forschungszentrum Berlin, Leibniz Institute, Berlin, GermanyDeutsches Rheuma-Forschungszentrum Berlin, Leibniz Institute, Berlin, GermanyCD4 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.03113/fullCD4 T cellsmemorybone marrowcell divisionmigration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jana Sarkander Shintaro Hojyo Mathias Mursell Yuzuru Yamasaki Tsung-Yen Wu Damon J. Tumes Kosuke Miyauchi Cam Loan Tran Jinfang Zhu Max Löhning Max Löhning Andreas Hutloff Mir-Farzin Mashreghi Masato Kubo Masato Kubo Andreas Radbruch Koji Tokoyoda |
spellingShingle |
Jana Sarkander Shintaro Hojyo Mathias Mursell Yuzuru Yamasaki Tsung-Yen Wu Damon J. Tumes Kosuke Miyauchi Cam Loan Tran Jinfang Zhu Max Löhning Max Löhning Andreas Hutloff Mir-Farzin Mashreghi Masato Kubo Masato Kubo Andreas Radbruch Koji Tokoyoda Enhanced Cell Division Is Required for the Generation of Memory CD4 T Cells to Migrate Into Their Proper Location Frontiers in Immunology CD4 T cells memory bone marrow cell division migration |
author_facet |
Jana Sarkander Shintaro Hojyo Mathias Mursell Yuzuru Yamasaki Tsung-Yen Wu Damon J. Tumes Kosuke Miyauchi Cam Loan Tran Jinfang Zhu Max Löhning Max Löhning Andreas Hutloff Mir-Farzin Mashreghi Masato Kubo Masato Kubo Andreas Radbruch Koji Tokoyoda |
author_sort |
Jana Sarkander |
title |
Enhanced Cell Division Is Required for the Generation of Memory CD4 T Cells to Migrate Into Their Proper Location |
title_short |
Enhanced Cell Division Is Required for the Generation of Memory CD4 T Cells to Migrate Into Their Proper Location |
title_full |
Enhanced Cell Division Is Required for the Generation of Memory CD4 T Cells to Migrate Into Their Proper Location |
title_fullStr |
Enhanced Cell Division Is Required for the Generation of Memory CD4 T Cells to Migrate Into Their Proper Location |
title_full_unstemmed |
Enhanced Cell Division Is Required for the Generation of Memory CD4 T Cells to Migrate Into Their Proper Location |
title_sort |
enhanced cell division is required for the generation of memory cd4 t cells to migrate into their proper location |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-01-01 |
description |
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. |
topic |
CD4 T cells memory bone marrow cell division migration |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.03113/full |
work_keys_str_mv |
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