Alloengraftment in IL-2-treated mice.
Despite major advances, graft-versus-host disease (GVHD) remains a major obstacle to clinical bone marrow transplantation. Prophylaxis by T cell depletion is associated with increased rates of engraftment failure and leukemic relapse. Treatment with high-dose IL-2 can markedly protect lethally irradiated mice from GVHD-related mortality, especially when T cell-depleted (TCD) syngeneic bone marrow cells (BMC) are co-administered. In these IL-2-protected animals, allogeneic reconstitution is observed, and a graft-versus-leukemia effect of allogeneic T cells is preserved. To determine whether IL-2 might increase alloresistance under conditions in which alloengraftment is more difficult to achieve, we have now evaluated the possible effect of IL-2 on: (1) competitive repopulation of lethally irradiated mice by mixtures of TCD allogeneic and TCD syngeneic BMC; (2) radiation protection by TCD allogeneic BMC; (3) timing of hematologic recovery; and (4) allogeneic engraftment in sublethally irradiated recipients. The results show that IL-2 has only a limited and strain-restricted effect on alloengraftment. This effect may reflect activation of alloresistant host natural killer cells, a cell population which is not essential for the protective effect of IL-2 against GVHD.
Sykes
M
M
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129.
Pearson
D A
DA
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010976:Platelet Count; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D007376:Interleukin-2