PREVENTION OF GRAFT-VERSUS-HOST DISEASE BY TREATMENT OF BONE MARROW WITH GLIOTOXIN IN FULLY ALLOGENEIC CHIMERAS AND THEIR CYTOTOXIC T CELL REPERTOIRE

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Abstract
Glitoxin, a secondary fungal metabolite, at nanomolar concentrations, irreversibly inhibits murine T cell proliferation to mitogen. Treatment of allogeneic spleen cells with gliotoxin allows their transfer into sublethally irradiated recipients without inducing a GVH reaction. Gliotoxin treatment of bone marrow allows the establishment of fully allogeneic bone marrow chimeras free of GVH disease. The cytotoxic T cell repertoire against influenza virus in these animals is restricted to both host- and donor-type MHC. However, their imune competence is severely compromised by their lack of host MHC-type stimulator cells.