Lethal graft-versus-host disease: modification with allogeneic cultured donor cells.
The use of the bone marrow culture technique was studied as a means to prepare donor marrow for bone marrow transplantation to avoid lethal graft-versus-host disease (GVHD). Preliminary experiments demonstrated the rapid loss of theta-positive cells in such cultures, so that theta-positive cells were not detected after 6 days. Initial experiments in C3H/HeJ (H-2k, Hbbd) recipients prepared with 900 rad demonstrated improved survival when 3-day cultured C57BL/6 (H-2b, Hbbs) donor cells were used in place of hind limb marrow for transplantation. However, hemoglobin typing of recipient animals revealed only short-term donor engraftment, with competitive repopulation of recipient marrow occurring. Subsequent experiments were done in 1,200-rad prepared recipients, with long-term donor engraftment demonstrated. The majority of 1,200-rad prepared animals receiving cultured allogeneic cells died of GVHD, but animals receiving 28-day cultured cells had an improved 90-day survival and a delay in GVHD development over animals receiving hind limb marrow or marrow from shorter times in culture. In addition, animals receiving anti-theta-treated, 3-day nonadherent cells had an improved survival (44%) over animals receiving anti-theta-treated hind limb marrow (20%). These experiments demonstrate modest benefit for the use of cultured cells in bone marrow transplantation across major H-2 histocompatibility complex differences.
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D001853:Bone Marrow / Q000276:immunology; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D006183:H-2 Antigens / Q000235:genetics; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera; D018800:Thy-1 Antigens; D014184:Transplantation, Homologous / Q000009:adverse effects*
D000954:Antigens, Surface; D006183:H-2 Antigens; D006454:Hemoglobins; D018800:Thy-1 Antigens