Prevention of acute graft-versus-host disease by treatment with a novel immunosuppressant. Cholera toxin B subunit.
Transplantation of allogeneic bone marrow (BM) is often complicated by the development of acute graft-vs-host disease (GVHD) caused by contaminating T cells in BM inocula because of activation of the host reactive T effector cells. Using a murine model for acute GVHD caused by injection of parental C57Bl/6 splenocytes into unirradiated (C57Bl/6 x DBA/2) F1 hybrids, we demonstrated that pretreatment of the inocula with a novel immunosuppressant, B subunit of cholera toxin (CT-B) impaired the ability of C57Bl/6 T cells to induce acute GVHD in F1 recipients. F1 mice injected with CT-B-treated C57Bl/6 splenocytes did not develop significant splenomegaly, and no antihost CTLs were found in their spleens. Moreover, these mice did not suffer from aplastic anemia, nor from general immunosuppression. Immunofluorescence studies suggest that treatment of the inducing inocula with CT-B selectively prevents accumulation of the host-reactive CD8+ T cells in F1 mice. Furthermore, our experiments demonstrated that CT-B treatment does not impair the ability of BM progenitors to form colonies in semisolid culture or in lethally irradiated hosts. Thus, taken together, our data suggest that ex vivo CT-B treatment can be used in allogeneic BM transplantation to prevent acute GVHD.
Yankelevich
B
B
Bone Marrow Transplantation, Program Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, DC 20007.
Brown
E
E
Mazumder
A
A
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002772:Cholera Toxin / Q000627:therapeutic use*; D003114:Colony-Forming Units Assay; D003208:Concanavalin A / Q000494:pharmacology; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D003208:Concanavalin A; D002772:Cholera Toxin