CXCR4, but not CXCR3, drives CD8(+) T-cell entry into and migration through the murine bone marrow
| Autor: | Graham Anderson, Mark Hoogenboezem, Edith Slot, Martijn A. Nolte, Marieke Goedhart, Stephanie Gessel, Carlijn Voermans, Jaap D. van Buul, Ellis Gielen, Sulima Geerman, Beth Lucas, Stephan Huveneers, Robbert van der Voort, Timo Rademakers, Harry Dolstra |
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| Přispěvatelé: | Graduate School, AII - Inflammatory diseases, Landsteiner Laboratory, Medical Biochemistry, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Clinical Haematology, CCA - Cancer biology and immunology |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
EXPRESSION Stromal cell Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] Immunology T cells EFFECTOR CHEMOKINE RECEPTOR CXCR3 Biology CXCR3 LYMPHOCYTES CXCR4 03 medical and health sciences Chemokine receptor All institutes and research themes of the Radboud University Medical Center 0302 clinical medicine medicine Immunology and Allergy Cytotoxic T cell Bone marrow HEMATOPOIETIC STEM-CELLS Migration IN-VIVO stromal cells MEMORY PROLIFERATION CXCL12 Cell biology 030104 developmental biology medicine.anatomical_structure MAINTENANCE SURVIVAL CD8 030215 immunology Homing (hematopoietic) |
| Zdroj: | European Journal of Immunology, 49, 576-589 European Journal of Immunology, 49(4), 576-589. Wiley European Journal of Immunology, 49, 4, pp. 576-589 European journal of immunology, 49(4), 576-589. Wiley-VCH Verlag |
| ISSN: | 0014-2980 |
| Popis: | The BM serves as a blood-forming organ, but also supports the maintenance and immune surveillance function of many T cells. Yet, in contrast to other organs, little is known about the molecular mechanisms that drive T-cell migration to and localization inside the BM. As BM accumulates many CXCR3-expressing memory CD8+ T cells, we tested the involvement of this chemokine receptor, but found that CXCR3 is not required for BM entry. In contrast, we could demonstrate that CXCR4, which is highly expressed on both naive and memory CD8+ T cells in BM, is critically important for homing of all CD8+ T-cell subsets to the BM in mice. Upon entry into the BM parenchyma, both naïve and memory CD8+ T cells locate close to sinusoidal vessels. Intravital imaging experiments revealed that CD8 T cells are surprisingly immobile and we found that they interact with ICAM-1+VCAM-1+BP-1+ perivascular stromal cells. These cells are the major source of CXCL12, but also express key survival factors and maintenance cytokines IL-7 and IL-15. We therefore conclude that CXCR4 is not only crucial for entry of CD8+ T cells into the BM, but also controls their subsequent localization toward BM niches that support their survival. |
| Databáze: | OpenAIRE |
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