An MHC-compatible allogeneic bone marrow donor with a distinct role of T cell subsets in graft-versus-leukemia effect and lethal graft-versus-host disease.
Our previous results in a murine model indicated that the GVL effect against radiation-induced leukemias could be induced in not only MHC-incompatible but also MHC-compatible allogeneic BMT, and that the intensity of the GVL effect induced in MHC-compatible allogeneic BMT varied among different leukemias and the donor/host strain combinations used. With the use of a radiation-induced T cell leukemia which followed the induction of the GVL effect in both MHC-compatible and -incompatible, allogeneic BMT, the role of T cell subsets in the development of the GVL effect and GVHD was studied. The results indicated that Lyt2+ T cells contaminating donor BM were consistently critical for the induction of the GVL effect in MHC-incompatible (B10) and -compatible (B10.BR and AKR) allogeneic BMT of leukemia-bearing C3H mice, but the depletion of L3T4+ T cells had no effect. In contrast, lethal GVHD induced by AKR donor lymph node cells was totally dependent on L3T4+ T cells, but the depletion of Lyt2+ T cells had no effect. On the other hand, both T cell subsets could cause lethal GVHD induced by MHC-incompatible (B10) and -compatible (B10.BR) allogeneic donors. The distinct roles of T cell subsets of AKR donors were confirmed by the preferential induction of the GVL effect with the AKR donor bone marrow mixed with lymph node cells which had been depleted of L3T4+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Physiology and Pathology, National Institute of Radiological Sciences, Chiba, Japan.
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Aizawa
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H
Kamisaku
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T
Sado
D000818:Animals; D000950:Antigens, Ly / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006086:Graft vs Host Disease / Q000209:etiology*; D007942:Leukemia, Experimental / Q000276:immunology* / Q000628:therapy; D008198:Lymph Nodes / Q000276:immunology; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D014184:Transplantation, Homologous
D000950:Antigens, Ly