Original Article

Bone Marrow Transplantation (2007) 40, 881–889; doi:10.1038/sj.bmt.1705819; published online 20 August 2007

Pre-Clinical Studies

Interleukin-7 induced facilitation of immunological reconstitution of sublethally irradiated mice following treatment with alloreactive spleen cells in a murine model of B-cell leukemia/lymphoma (BCL1)

A Abdul-Hai1, L Weiss1, A Ben-Yehuda2, D Ergas3, M Y Shapira1 and S Slavin1

  1. 1Department of Bone Marrow Transplantation and Cancer Immunotherapy, Cell Therapy and Transplantation Research Center, Hadassah University Hospital, Jerusalem, Israel
  2. 2Department of Internal Medicine, Hebrew University—Hadassah School of Medicine, Jerusalem, Israel
  3. 3Department of Internal Medicine, Hebrew University—Hadassah School of Medicine, Kaplan School of Medicine, Jerusalem, Israel

Correspondence: Dr S Slavin, Department of Bone Marrow Transplantation and Cancer Immunotherapy, Cell Therapy and Transplantation Research Center, Hadassah University Hospital, POB 12000, Jerusalem 91120, Israel. E-mail: slavin@cc.huji.ac.il

Received 15 March 2007; Revised 31 May 2007; Accepted 3 July 2007; Published online 20 August 2007.

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Abstract

Interleukin-7 (IL-7) plays a key role in maturation and function of both T and B cells. We investigate the potential use of recombinant human IL-7 for facilitation of graft-versus-leukemia (GVL) effects mediated by T cells following transplantation in a murine model. Administration of IL-7 in vivo to allogeneic-transplanted mice improved disease-free survival: 67% of mice treated with IL-7 remained alive and disease free for more than 60 days, in comparison to 17% of the controls (P<0.05). Similar results were obtained when C57BL/6 spleen cells sensitized against irradiated B-cell leukemia (BCL1) cells in the presence of IL-7 were transplanted to F1 mice, followed by IL-7 treatment in vivo. Of the BALB/c mice that received spleen cells from F1 mice treated with IL-7 following transplantation of C57BL/6 spleen cells sensitized with irradiated BCL1 in the presence of IL-7, only 29% developed leukemia, as compared to 79% in the control group (P<0.05). Mice treated with IL-7 showed increased splenic and thymic cellularity and improved T cell-dependent proliferative responses compared to the controls (P<0.05). IL-7 may provide a novel tool to enhance immune reconstitution following transplantation of mismatched stem cells and for enhancement of GVL effects mediated by alloreactive lymphocytes.

Keywords:

interleukin-7, spleen cells, GVL, immune reconstitution

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