Interleukin-15 enhances immune reconstitution after allogeneic bone marrow transplantation.
Interleukin-15 (IL-15) is a gamma-common cytokine that plays an important role in the development, survival, and proliferation of natural killer (NK), NK T, and CD8+ T-cells. We administered IL-15 to recipients of an allogeneic bone marrow transplantation (allo BMT) to determine its effects on immune reconstitution. Posttransplantation IL-15 administration significantly increased donor-derived CD8+ T (mostly CD122(+)CD44(+)CD8+ T-cells), NK, and NK T-cells at day +28 in young and old recipients of allo BMT. This was associated with enhanced T-cell and NK-cell function. IL-15 stimulated homeostatic proliferation of donor CD8+ T-cells in recipients of carboxyfluorescein diacetate succinimidyl ester-labeled donor T-cell infusions. Posttransplantation IL-15 administration also resulted in a decrease in apoptotic CD8+ T-cells, an increase in Bcl-2-expressing CD8+ T-cells, and an increase in the fraction of Ki67+ proliferative NK and CD8+ T-cells in recipients of allo BMT. IL-15 did not exacerbate graft-versus-host disease (GVHD) in recipients of T-cell-depleted BMT but could aggravate GVHD in some cases in recipients of a T-cell-repleted BMT. Finally, we found that IL-15 administration could enhance graft-versus-leukemia activity. In conclusion, IL-15 can be administered safely to recipients of a T-cell-depleted allo BMT to enhance CD8+ T, NK, and NK T-cell reconstitution.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Onder
O
Alpdogan
Jeffrey M
JM
Eng
Stephanie J
SJ
Muriglan
Lucy M
LM
Willis
Vanessa M
VM
Hubbard
Kartono H
KH
Tjoe
Theis H
TH
Terwey
Adam
A
Kochman
Marcel R M
MR
van den Brink
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology; D018960:Hyaluronan Receptors / Q000378:metabolism; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014184:Transplantation, Homologous
D018960:Hyaluronan Receptors; D019409:Interleukin-15; D015375:Receptors, Interleukin-2