PMID- 9212108
OWN - NLM
STAT- MEDLINE
DCOM- 19970804
LR  - 20190914
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 3
IP  - 7
DP  - 1997 Jul
TI  - Induction of high levels of allogeneic hematopoietic reconstitution and 
      donor-specific tolerance without myelosuppressive conditioning.
PG  - 783-7
AB  - Donor-specific tolerance induced by bone marrow transplantation (BMT) would allow 
      organ allografting without chronic immunosuppressive therapy. However, the 
      toxicity of conditioning regimens used to achieve marrow engraftment has 
      precluded the clinical use of BMT for tolerance induction. We have developed a 
      BMT strategy that achieves alloengraftment without toxic or myelosuppressive host 
      conditioning. B6 mice received depleting anti-CD4 and anti-CD8 monoclonal 
      antibodies, local thymic irradiation, and a high-dose (174 x 10(6)) of major 
      histocompatibility (MHC)-mismatched B10.A bone marrow cells (BMCs) divided over 
      days 0 through 4. High levels of donor cells were observed among white blood 
      cells (WBCs) of all lineages. Permanent, multilineage mixed chimerism; 
      donor-specific skin-graft tolerance; and in vitro tolerance were observed in most 
      animals. Large numbers of donor class II(high) cells were detected in thymuses of 
      long-term chimeras, and their presence was associated with intrathymic deletion 
      of donor-reactive host thymocytes. The treatment was not associated with 
      significant myelosuppression, toxicity, or graft-versus-host disease (GVHD). 
      Thus, high levels of allogeneic stem-cell engraftment can be achieved without 
      myelosuppressive host conditioning. As stem-cell mobilization and in vitro 
      culture techniques have increased the feasibility of administering high doses of 
      hematopoietic cells to humans, this approach brings hematopoietic cell 
      transplantation closer to clinical use for the induction of central deletional 
      T-cell tolerance.
FAU - Sykes, M
AU  - Sykes M
AD  - Transplantation Biology Research Center, Surgical Service, Massachusetts General 
      Hospital/Harvard Medical School, Boston 02129, USA.
FAU - Szot, G L
AU  - Szot GL
FAU - Swenson, K A
AU  - Swenson KA
FAU - Pearson, D A
AU  - Pearson DA
LA  - eng
GR  - R01-HL-18646/HL/NHLBI NIH HHS/United States
GR  - R01-HL-49915/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antilymphocyte Serum)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*administration & dosage/immunology
MH  - Antilymphocyte Serum/*administration & dosage/immunology
MH  - B-Lymphocytes/cytology
MH  - Bone Marrow Transplantation/*immunology
MH  - CD4-Positive T-Lymphocytes/cytology/immunology
MH  - CD8-Positive T-Lymphocytes/cytology/immunology
MH  - Female
MH  - Graft Survival
MH  - *Hematopoietic Stem Cells
MH  - Humans
MH  - *Immune Tolerance
MH  - Lymphocyte Count
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Receptors, Antigen, T-Cell, alpha-beta/analysis
MH  - Transplantation Chimera
MH  - *Transplantation Conditioning/methods
MH  - Transplantation, Homologous
EDAT- 1997/07/01 00:00
MHDA- 1997/07/01 00:01
CRDT- 1997/07/01 00:00
PHST- 1997/07/01 00:00 [pubmed]
PHST- 1997/07/01 00:01 [medline]
PHST- 1997/07/01 00:00 [entrez]
AID - 10.1038/nm0797-783 [doi]
PST - ppublish
SO  - Nat Med. 1997 Jul;3(7):783-7. doi: 10.1038/nm0797-783.