Prevention of graft-versus-host disease by treatment of bone marrow with gliotoxin in fully allogeneic chimeras and their cytotoxic T cell repertoire.
Gliotoxin, 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 allogenic 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 immune competence is severely compromised by their lack of host MHC-type stimulator cells.
Müllbacher
A
A
Department of Microbiology, John Curtin School of Medical Research, Australian National University, Canberra.
Moreland
A F
AF
Waring
P
P
Sjaarda
A
A
Eichner
R D
RD
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D005260:Female; D005912:Gliotoxin / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D007111:Immunity, Cellular; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009183:Mycotoxins / Q000627:therapeutic use*; D009975:Orthomyxoviridae / Q000276:immunology; D011828:Radiation Chimera; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D009183:Mycotoxins; D005912:Gliotoxin