Chemokine treatment rescues profound T-lineage progenitor homing defect after bone marrow transplant conditioning in mice
| Autor: | Bruce R. Blazar, Avinash Bhandoola, Jerrod L. Bryson, Daniel A. Zlotoff, Xinxin Wang, Sugata Manna, Shirley L. Zhang |
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| Rok vydání: | 2014 |
| Předmět: |
Chemokine
Transplantation Conditioning T-Lymphocytes Immunology chemical and pharmacologic phenomena Mice Transgenic Thymus Gland Biochemistry Mice immune system diseases Cell Movement hemic and lymphatic diseases medicine Animals Cell Lineage Progenitor cell Cells Cultured Progenitor Bone Marrow Transplantation Transplantation biology Chemokine CCL21 hemic and immune systems Cell Biology Hematology Lymphoid Progenitor Cells Mice Inbred C57BL medicine.anatomical_structure surgical procedures operative Chemokines CC biology.protein Cancer research Female Bone marrow CCL25 CCL21 Homing (hematopoietic) |
| Zdroj: | Blood. 124(2) |
| ISSN: | 1528-0020 |
| Popis: | Development of T cells in the thymus requires continuous importation of T-lineage progenitors from the bone marrow via the circulation. Following bone marrow transplant, recovery of a normal peripheral T-cell pool depends on production of naive T cells in the thymus; however, delivery of progenitors to the thymus limits T-lineage reconstitution. Here, we examine homing of intravenously delivered progenitors to the thymus following irradiation and bone marrow reconstitution. Surprisingly, following host conditioning by irradiation, we find that homing of lymphoid-primed multipotent progenitors and common lymphoid progenitors to the thymus decreases more than 10-fold relative to unirradiated mice. The reduction in thymic homing in irradiated mice is accompanied by a significant reduction in CCL25, an important chemokine ligand for thymic homing. We show that pretreatment of bone marrow progenitors with CCL25 and CCL21 corrects the defect in thymic homing after irradiation and promotes thymic reconstitution. These data suggest new therapeutic approaches to promote T-cell regeneration. |
| Databáze: | OpenAIRE |
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