Interleukin-1 alpha-mediated promotion of long-term alloengraftment and short-term neutrophil expansion does not require the presence of either donor or host T cells.
In earlier studies, we showed that a 14-day continuous subcutaneous infusion of recombinant human interleukin (IL)-1 accelerated neutrophil recovery and enhanced long-term chimerism in a bone marrow (BM) transplant model in which T-cell-depleted BALB/c donor BM was given to irradiated C57BL/6 fully allogeneic recipients. We have extended these studies to a model entirely devoid of donor and host T cells. In the model, donor BALB/c congenic severe combined immunodeficient (C.B-17-scid/scid) BM cells are T cell depleted. The cells are then transplanted into adult irradiated C57BL/6 hosts that have been thymectomized and treated with anti-CD4 and CD8. When IL-1 alpha was delivered subcutaneously using a mini-osmotic pump, it enhanced short-term neutrophil recovery and longer term alloengraftment despite the absence of T cells in the donors and the hosts. Therefore, T cells were not required for the promotional effects of IL-1 alpha on neutrophil recovery and alloengraftment. Studies also showed that the potency of the IL-1 alpha effects was related to the degree of donor cell engraftment, which was related to the irradiation dose and the presence of T cells. We conclude that IL-1 alpha can augment post-BM transplantation hematopoietic recovery and alloengraftment via a T-cell-independent mechanism by favoring donor allogeneic hematopoietic progenitor cell competition over limited numbers of host progenitor cells.
Vallera
D A
DA
Department of Therapeutic Radiology, University of Minnesota Cancer Center, Minneapolis 55455, USA. valle001.maroon.tc.umn.edu
Taylor
P A
PA
Widmer
M B
MB
Blazar
B R
BR
D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects*; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D014916:Whole-Body Irradiation
D007375:Interleukin-1