Combined Effects of Interleukin-7 and Stem Cell Factor Administration on Lymphopoiesis after Murine Bone Marrow Transplantation

• Published in: Biology of blood and marrow transplantation 2011, Vol.17 (1), p.48-60
• Main Authors: Chung, Brile, Min, Dullei, Joo, Lukas W, Krampf, Mark R, Huang, Jing, Yang, Yujun, Shashidhar, Sumana, Brown, Janice, Dudl, Eric P, Weinberg, Kenneth I
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Transplantation - methods; Cell Proliferation - drug effects; Drug Synergism; Drug Therapy, Combination; Hematology, Oncology and Palliative Medicine; Humans; Immune System - drug effects; Immune System - physiology; Interleukin-7; Interleukin-7 - administration & dosage; Interleukin-7 - pharmacology; Lymphopoiesis - drug effects; Mice; Murine bone marrow transplantation; Stem cell factor; Stem Cell Factor - administration & dosage; Stem Cell Factor - pharmacology; Thymus Gland - cytology; Treatment Outcome
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2010.07.027

The decreased ability of the thymus to generate T cells after bone marrow transplantation (BMT) is a clinically significant problem. Interleukin (IL)-7 and stem cell factor (SCF) induce proliferation, differentiation, and survival of thymocytes. Although previous studies have shown that administration of recombinant human IL-7 (rhIL-7) after murine and human BMT improves thymopoiesis and immune function, whether administration of SCF exerts similar effects is unclear. To evaluate independent or combinatorial effects of IL-7 and SCF in post-BMT thymopoiesis, bone marrow (BM)-derived mesenchymal stem cells transduced ex vivo with the rhIL-7 or murine SCF (mSCF) genes were cotransplanted with T cell–depleted BM cells into lethally irradiated mice. Although rhIL-7 and mSCF each improved immune reconstitution, the combination treatment had a significantly greater effect than either cytokine alone. Moreover, the combination treatment significantly increased donor-derived common lymphoid progenitors (CLPs) in BM, suggesting that transplanted CLPs expand more rapidly in response to IL-7 and SCF and may promote immune reconstitution. Our findings demonstrate that IL-7 and SCF might be therapeutically useful for enhancing de novo T cell development. Furthermore, combination therapy may allow the administration of lower doses of IL-7, thereby decreasing the likelihood of IL-7–mediated expansion of mature T cells.