Mechanism of protection from graft-versus-host disease mortality by IL-2. III. Early reductions in donor T cell subsets and expansion of a CD3+CD4-CD8- cell population.
Reducing the graft-vs-host disease (GVHD)-promoting capacity of allogeneic T cells while maintaining alloengraftment and graft-vs-leukemia effects remains an important but elusive goal in clinical bone marrow transplantation (BMT). We have recently demonstrated that a short course of high dose IL-2 administered at the time of BMT has a powerful protective effect against GVHD mortality in mice. This short course of IL-2 is able to protect mice from both acute and chronic GVHD without sacrificing alloengraftment or graft-vs-leukemia effects of allogeneic T cells. Because the early administration of IL-2 seems to be crucial for this effect, we have studied the early lymphoid repopulation events after lethal irradiation and allogeneic BMT. These studies show that there are consistent delays in splenic repopulation by allogeneic cells after BMT in IL-2-treated animals compared with their untreated cohorts. Even greater percent reductions were seen in donor splenic T cell populations in the first few days after BMT in IL-2-treated animals. Splenic cells with the CD3+CD4-CD8- phenotype were increased in IL-2 treated animals at days 3 and 4 after BMT. This phenotype resembles that of bone marrow-derived cells which have been previously shown to inhibit GVHD, suggesting a possible mechanism for the protective effect of IL-2.
Abraham
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VS
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129.
Sachs
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DH
Sykes
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D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000276:immunology*; D017252:CD3 Complex; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D007376:Interleukin-2 / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D011828:Radiation Chimera / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013154:Spleen / Q000166:cytology; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell