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- Title
Interleukin-15 administration increases graft-versus-tumor activity in recipients of haploidentical hematopoietic SCT.
- Authors
Sauter, C T; Bailey, C P; Panis, M M; Biswas, C S; Budak-Alpdogan, T; Durham, A; Flomenberg, N; Alpdogan, O
- Abstract
Utilizing a clinically relevant haploidentical (HI) murine transplant model, lethally irradiated B6D2F1 (H2Kb/d) mice were transplanted with T cell-depleted (TCD) BM from B6CBAF1 (H2Kb/k) mice. We found that administration of IL-15 significantly increases the numbers of CD8+ T and natural killer (NK) cells in spleen and BM after transplantion without GVHD. Graft-versus-tumor (GVT) potency of the graft was evaluated upon tumor challenge using P815 tumor cells (H2d). IL-15 administration without T-cell infusion did not result in any survival improvement. However, IL-15 in combination with very low-dose T-cell infusion (1 × 104) significantly increased GVT activity and improved survival in recipients of HI hematopoietic SCT (HSCT). This effect was observed when IL-15 was given at a later time point, rather than immediately following transplantation. IL-15 administration also specifically increased slow-proliferative CD8+ T-cell proliferation and IFN-γ secretion in CD8+ T cells in recipients of CFSE (carboxyfluorescein succinimidyl ester)-labeled HI T-cell infusion, whereas there was no effect on CD4+ T-cell proliferation, suggesting the critical effect of IL-15 on CD8+ T-cell homeostasis in HI host. We conclude that IL-15 can be used for enhancing antileukemia effect of HI-HSCT, which requires presence of donor-derived T cells.
- Subjects
INTERLEUKIN-15; HEMATOPOIETIC stem cell transplantation; CYTOKINES; CELL proliferation; T cells
- Publication
Bone Marrow Transplantation, 2013, Vol 48, Issue 9, p1237
- ISSN
0268-3369
- Publication type
Article
- DOI
10.1038/bmt.2013.47