Evidence that residual host cells surviving the conditioning regimen to allogeneic bone marrow transplantation inhibit donor hematopoiesis in vitro--the role of TNF-alpha.
Blood cells were obtained from patients selected for allogeneic bone marrow transplantation who had undergone a conditioning regimen (CR) with high-dose chemotherapy and total body irradiation. The majority of residual cells bore CD3 antigen (range: 68-98%), and the CD4/CD8 ratio was normal. The effect of these residual/radioresistant cells on donor bone marrow hematopoiesis was investigated in eleven cases. Growth of donor CFU-GM and BFU-E was inhibited by 22-65% and 29-77%, respectively, when donor marrow was cocultured with residual cells at various ratios. In contrast, blood cells obtained from two patients prior to CR had no inhibitory effect. Supernatants obtained following incubation of residual cells from 9 patients were able to inhibit the growth of CFU-GM and BFU-E from normal unrelated subjects, whereas supernatants obtained before CR and from cultured normal marrow had no inhibitory effect. In addition, in blocking experiments, an anti-TNF-alpha MoAb was able to prevent this inhibition. Thus, TBI might be able to select and/or activate cells responsible for hematopoietic growth inhibition by a mechanism involving, at least in part, TNF-alpha.
Vinci
G
G
Bone Marrow Transplantation Unit, Hopital Henri Mondor, Creteil, Paris, France.
Chouaib
S
S
Autran
B
B
Vernant
J P
JP
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016026:Bone Marrow Transplantation; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D008297:Male; D051381:Rats; D013601:T-Lymphocytes / Q000502:physiology; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha