Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7
| Autor: | Kenneth I. Weinberg, Ellen Bolotin, Monika Smogorzewska, Susan Smith, Michael Widmer |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Male
Receptors Antigen T-Cell alpha-beta T cell Immunology Thymus Gland Biology Hematopoietic Cell Growth Factors Lymphocyte Activation Biochemistry Andrology Mice T-Lymphocyte Subsets medicine Animals Lymphocyte Count Lymphopoiesis Gene Rearrangement beta-Chain T-Cell Antigen Receptor Bone Marrow Transplantation Interleukin-7 Cell Cycle Graft Survival Immunologic Deficiency Syndromes Interleukin Gene rearrangement Cell Biology Hematology medicine.disease Stimulation Chemical Hematopoiesis Mice Inbred C57BL Haematopoiesis medicine.anatomical_structure surgical procedures operative Leukopoiesis Radiation Chimera Thymic hypoplasia Female Bone marrow Spleen |
| Zdroj: | Blood. 88:1887-1894 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v88.5.1887.bloodjournal8851887 |
| Popis: | Bone marrow transplantation (BMT) is followed by a period of profound immune deficiency, during which new T lymphocytes are generated from either stem cells or immature thymic progenitors. Interleukin-7 (IL-7) induces proliferation and differentiation of immature thymocytes. We examined whether the in vivo administration of IL-7 to mice receiving BMT would alter thymic reconstitution. Lethally irradiated C57BL/6 mice received syngeneic BMT, followed by either IL-7 or placebo from days 5 to 18 post-BMT. At day 28, BMT recipients that had not received IL-7 had profound thymic hypoplasia (< 5% of normal), with relative increases in the numbers of immature thymocytes, decreased numbers of mature peripheral (splenic) T lymphocytes, and severely impaired T- and B-cell function. In contrast, transplanted mice treated with IL-7 had normalization of thymic cellularity, with normal proportions of thymic subsets and T-cell receptor beta variable gene (TCRV beta) usage, normal numbers of peripheral CD4+ T lymphocytes, and improved antigen- specific T- and B-cell function. In the BMT-IL-7 mice, there was an eightfold increase in the number of immature CD3-CD4-CD8- thymocytes in G2-M of the cell cycle, indicating that restoration of thymic cellularity was due to enhanced proliferation of immature thymic progenitors. Similar effects following IL-7 administration were also observed when donor bone marrow was depleted of mature T lymphocytes, indicating that IL-7 administration affected immature hematopoietic progenitors. IL-7 promotes thymic reconstitution after BMT, and may be useful in preventing post-BMT immune deficiency. |
| Databáze: | OpenAIRE |
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