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).
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 (BCL(1)) cells in the presence of IL-7 were transplanted to F(1) mice, followed by IL-7 treatment in vivo. Of the BALB/c mice that received spleen cells from F(1) mice treated with IL-7 following transplantation of C57BL/6 spleen cells sensitized with irradiated BCL(1) 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.
Abdul-Hai
A
A
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Cell Therapy and Transplantation Research Center, Hadassah University Hospital, Jerusalem, Israel.
Weiss
L
L
Ben-Yehuda
A
A
Ergas
D
D
Shapira
M Y
MY
Slavin
S
S
D019264:Adoptive Transfer; D000818:Animals; D017690:Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D018572:Disease-Free Survival; D020544:Graft vs Leukemia Effect / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000502:physiology*; D015851:Interleukin-7 / Q000494:pharmacology / Q000627:therapeutic use*; D015448:Leukemia, B-Cell / Q000628:therapy*; D016393:Lymphoma, B-Cell / Q000628:therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D012038:Regeneration / Q000187:drug effects; D013154:Spleen / Q000166:cytology*; D014184:Transplantation, Homologous
D015851:Interleukin-7