Antibody and pre- plus post-transplant prednisone treatments support T cell-depleted stem cell engraftment without drug-induced morbidity.
Rigorous T cell depletion methods can now be used to reduce the risk of graft-versus-host disease (GVHD) associated with allogeneic, hematopoietic stem cell transplantation (HSCT). However, full T cell depletion is also associated with a significant risk of graft failure. Here we hypothesize that engraftment failures after T cell-depleted HSCT may be due, in part, to the absence of GVHD prophylaxis. To test this hypothesis, we used a haploidentical mouse model to systematically measure the effects of immunosuppressive drug treatments and anti-T cell antibodies on engraftment. Results showed that engraftment was supported in all animals when hosts were pre-treated with anti-T cell antibodies, but donor chimerism was significantly improved when hosts were also treated with prednisone. Interestingly, when hosts received only pre-HSCT prednisone treatments, engraftment was not improved; when hosts received only post-HSCT prednisone (initiated near the time of irradiation), the animals became extremely ill. Results therefore demonstrated the need for both pre- and post-HSCT prednisone treatments as a means to ensure engraftment without morbidity in all host animals.
D'Costa
S
S
Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Hurwitz
J L
JL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D018106:CD28 Antigens / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D004334:Drug Administration Schedule; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D008212:Lymphocyte Depletion / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D011828:Radiation Chimera; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D014916:Whole-Body Irradiation / Q000009:adverse effects
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D015704:CD4 Antigens; D007166:Immunosuppressive Agents; D011241:Prednisone