Newborn blood used as a source of donor cells in a murine model of transplantation across non-MHC antigens.
Cells derived from human cord blood instead of bone marrow were recently used for transplantation. However, several questions concerning the potential of this source of cells to reconstitute the hematopoietic and immunologic system of the recipient and to induce graft-versus-host disease (GVHD) remain unanswered. We used newborn blood (NBB) cells from B10.D2 mice to engraft lethally irradiated (DBA/2 x B10.D2)F1 recipients incompatible for multiple non-H-2 antigens. The median volume of NBB collected from one mouse ranged between 40 and 50 microliters and the number of nucleated cells was approximately 4-5 x 10(5) per sample. We first established that NBB contains around 10-20% of stem cells (SCA-1+) and 30% of CD4+CD8+ Thy-1+ immature T cells. The injection of blood pooled from one to three newborn mice resulted in engraftment of 71%-86% of F1 recipients that survived more than 100 days. Long-term surviving mice exhibited mixed chimerism (approximately 69% of cells of donor origin) 2-4 months after transplantation, and clinical signs of GVHD across minor histocompatibility Ags (mHAgs) were never observed. Additionally, mixed lymphocyte reaction and cytotoxic assay responses of those mice against host antigens were undetectable, while reactivity against unrelated H-2 Ag was normal. The establishment of host-specific tolerance in NBB engrafted mice was confirmed by in vivo transfer experiments. In conclusion, NBB cells reconstituted the lymphohematopoietic system of lethally irradiated mice without inducing GVHD. However, the question of the presence of an active antileukemic effect remains to be answered.
de la Selle
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V
INSERM U267, Groupe hospitalier Paul Brousse, Villejuif, France.
Bruley-Rosset
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M
D000818:Animals; D000831:Animals, Newborn / Q000097:blood*; D002469:Cell Separation; D005434:Flow Cytometry; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006648:Histocompatibility; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018183:Transplantation Chimera
D006183:H-2 Antigens; D015778:Minor Histocompatibility Antigens