INTERLEUKIN-1??-MEDIATED PROMOTION OF LONG-TERM ALLOENGRAFTMENT AND SHORT-TERM NEUTROPHIL EXPANSION DOES NOT REQUIRE THE PRESENCE OF EITHER DONOR OR HOST T CELLS1

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Abstract
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.

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