Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7.
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.
Bolotin
E
E
Department of Pediatrics, Childrens Hospital Los Angeles, University of Southern California School of Medicine, Los Angeles, USA.
Smogorzewska
M
M
Smith
S
S
Widmer
M
M
Weinberg
K
K
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002453:Cell Cycle; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006085:Graft Survival / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*; D007153:Immunologic Deficiency Syndromes / Q000209:etiology / Q000517:prevention & control; D015851:Interleukin-7 / Q000494:pharmacology / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013154:Spleen / Q000473:pathology; D013268:Stimulation, Chemical; D016176:T-Lymphocyte Subsets / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology
D016298:Hematopoietic Cell Growth Factors; D015851:Interleukin-7; D016693:Receptors, Antigen, T-Cell, alpha-beta