Combined effects of interleukin-7 and stem cell factor administration on lymphopoiesis after murine bone marrow transplantation.
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.
Chung
Brile
B
Division of Stem Cell Transplantation, Department of Pediatric and Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, California 94304, USA.
Min
Dullei
D
Joo
Lukas W
LW
Krampf
Mark R
MR
Huang
Jing
J
Yang
Yujun
Y
Shashidhar
Sumana
S
Brown
Janice
J
Dudl
Eric P
EP
Weinberg
Kenneth I
KI
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000502:physiology; D015851:Interleukin-7 / Q000008:administration & dosage* / Q000494:pharmacology; D038041:Lymphopoiesis / Q000187:drug effects*; D051379:Mice; D019089:Stem Cell Factor / Q000008:administration & dosage* / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology; D016896:Treatment Outcome
D015851:Interleukin-7; D019089:Stem Cell Factor