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 Blood, 15 January 2005, Vol. 105, No. 2, pp. 865-873.
Prepublished online as a Blood First Edition Paper on July 27, 2004; DOI 10.1182/blood-2003-09-3344.

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Submitted September 29, 2003
Accepted June 30, 2004

Interleukin-15 enhances immune reconstitution after allogeneic bone marrow transplantation

Onder Alpdogan, Jeffrey M Eng, Stephanie J Muriglan, Lucy M Willis, Vanessa M Hubbard, Kartono H Tjoe, Theis H Terwey, Adam Kochman, and Marcel R van den Brink*

Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

* Corresponding author; email: vandenbm{at}mskcc.org.

Interleukin-15 (IL-15) is a {gamma}-common cytokine, which plays an important role in the development, survival and proliferation of 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. Post-transplant 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 CFSE-labeled donor T cell infusions. Post-transplant 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 (GVL) 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.


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