PMID- 12152983
OWN - NLM
STAT- MEDLINE
DCOM- 20030113
LR  - 20211203
IS  - 1042-8194 (Print)
IS  - 1026-8022 (Linking)
VI  - 43
IP  - 6
DP  - 2002 Jun
TI  - Induction of immunologic tolerance for allogeneic hematopoietic cell 
      transplantation.
PG  - 1159-67
AB  - The ability to achieve complete hematopoietic engraftment in the allogeneic 
      setting without intensive myeloablative chemotherapy will have a profound effect 
      on the practice of allogeneic hematopoietic cell transplantation (HCT). Novel 
      methods to induce antigen-specific T-cell tolerance provide promise to ensure 
      engraftment and reduce GVHD without producing generalized and other toxicities 
      caused by myeloablative conditioning regimens. Compelling experimental evidence 
      indicates that the antigen receptors on T-lymphocytes have dual potential to 
      transmit crucial activation signals for initiating immune responses and to 
      discharge equally potent inactivating signals to abort or inhibit immune 
      responses. Many events impact on this fundamental decision-making process and one 
      of the great challenges for modern immunology is to decipher the molecular wiring 
      that integrates and converts the extrinsic and intrinsic variables into positive 
      or negative cellular responses termed immunity and anergy, respectively. Our 
      currently expanding understanding of the biochemical and molecular basis of 
      T-cell anergy provides great promise to improve our ability to design novel 
      clinical therapeutic approaches in order to induce antigen-specific tolerance in 
      vivo. Importantly, strategies now exist to segregate graft versus tumor (GVT) 
      effects from GVHD. Therefore, achievement of limited and specific tolerance to 
      host alloantigens by selectively inactivating the indicated subsets of 
      alloantigen-specific T-lymphocytes will prevent GVHD but retain the GVT effect of 
      the graft. Such treatment approaches will expand the donor pool, because they 
      will allow transplantation between individuals with increasing human leukocyte 
      antigen (HLA) disparity, enable reduction of the need for non-specific 
      immunosuppression, and reduce the risk of opportunistic infections and relapse of 
      leukemia.
FAU - Appleman, Leonard J
AU  - Appleman LJ
AD  - Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, 
      USA.
FAU - Tzachanis, Dimitrios
AU  - Tzachanis D
FAU - Grader-Beck, Thomas
AU  - Grader-Beck T
FAU - Van Puijenbroek, Andre A F L
AU  - Van Puijenbroek AA
FAU - Boussiotis, Vassiliki A
AU  - Boussiotis VA
LA  - eng
GR  - AI41584/AI/NIAID NIH HHS/United States
GR  - AI43552/AI/NIAID NIH HHS/United States
GR  - AI46548/AI/NIAID 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.
PT  - Review
PL  - United States
TA  - Leuk Lymphoma
JT  - Leukemia & lymphoma
JID - 9007422
RN  - 0 (Antigens, CD)
RN  - 0 (B7-1 Antigen)
RN  - 0 (B7-2 Antigen)
RN  - 0 (CD28 Antigens)
RN  - 0 (CD40 Antigens)
RN  - 0 (CD86 protein, human)
RN  - 0 (Cd86 protein, mouse)
RN  - 0 (Cdkn1b protein, mouse)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Immunoconjugates)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 7D0YB67S97 (Abatacept)
SB  - IM
MH  - Abatacept
MH  - Animals
MH  - Antigens, CD/physiology
MH  - B7-1 Antigen/physiology
MH  - B7-2 Antigen
MH  - CD28 Antigens/physiology
MH  - CD40 Antigens/physiology
MH  - CD40 Ligand/physiology
MH  - Cell Cycle Proteins/physiology
MH  - Clonal Anergy
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - Graft vs Host Disease/prevention & control
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Histocompatibility
MH  - Humans
MH  - Immunoconjugates/pharmacology
MH  - Immunosuppression Therapy/*methods
MH  - Lymphocyte Depletion
MH  - Membrane Glycoproteins/antagonists & inhibitors/physiology
MH  - Mice
MH  - Receptors, Antigen, T-Cell/immunology
MH  - T-Lymphocytes/immunology
MH  - Transplantation, Homologous/*immunology
MH  - Tumor Suppressor Proteins/physiology
RF  - 73
EDAT- 2002/08/03 10:00
MHDA- 2003/01/14 04:00
CRDT- 2002/08/03 10:00
PHST- 2002/08/03 10:00 [pubmed]
PHST- 2003/01/14 04:00 [medline]
PHST- 2002/08/03 10:00 [entrez]
AID - 10.1080/10428190290026213 [doi]
PST - ppublish
SO  - Leuk Lymphoma. 2002 Jun;43(6):1159-67. doi: 10.1080/10428190290026213.