PMID- 15385803
OWN - NLM
STAT- MEDLINE
DCOM- 20041208
LR  - 20190713
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 78
IP  - 6
DP  - 2004 Sep 27
TI  - Induction of xenogeneic neonatal tolerance to transgenic human leukocyte antigen 
      class I grafts.
PG  - 844-52
AB  - BACKGROUND: The immune response against xenografts is vigorous and poorly 
      controlled with conventional immunosuppressants. Therefore, success in 
      xenotransplantation will depend on developing additional approaches such as 
      induction of immunologic unresponsiveness or tolerance. Although classic 
      protocols of neonatal tolerance induction in mice are very tolerogenic in many 
      allogeneic models, they have generally failed in xenogeneic models. The purpose 
      of these studies was to determine whether failure results from an intrinsic 
      property of xenogenic major histocompatibility complex (MHC) molecules themselves 
      or, instead, is caused by some limitation in species-specific molecular 
      interactions distinct from the polymorphic domains of xenogenic MHC molecules. 
      METHODS: Our approach was to test the ability of lymphoid cells from a transgenic 
      (Tg) mouse donor expressing a xeno-MHC class I molecule encoding the polymorphic 
      alpha1/alpha2 for human leukocyte antigen (HLA)-B7 to induce neonatal tolerance 
      in non-Tg syngeneic C57BL/6 recipients. Because the donor and recipient strains 
      are genetically identical (C57BL/6, H-2b) except for Tg human MHC HLA-B7, any 
      species-specific molecular incompatibility in this mouse anti-human class I 
      xeno-combination that could potentially interfere with induction of tolerance has 
      been eliminated. RESULTS: Our results show that HLA-B7 Tg-, but not C57BL/6 
      syngeneic-, injected neonates were unresponsive as adults to HLA-B7-expressing 
      target cells in vitro and specifically accepted HLA-B7-expressing Tg skin grafts. 
      In addition, neonatal injection of donor cells resulted in peripheral chimerism. 
      CONCLUSIONS: These experiments demonstrate that, as long as species-specific 
      molecular interactions are maintained, recognition of the polymorphic domains of 
      xenogeneic MHC does not represent a barrier to neonatal tolerance induction.
FAU - Borenstein, Steven H
AU  - Borenstein SH
AD  - Research Institute, Program in Infection, Immunity, Injury and Repair, The 
      Hospital for Sick Children, Toronto, Ontario, Canada.
FAU - Tao, Kesheng S
AU  - Tao KS
FAU - Mendicino, Michael
AU  - Mendicino M
FAU - Hu, Ningjie
AU  - Hu N
FAU - West, Lori J
AU  - West LJ
FAU - Chamberlain, John W
AU  - Chamberlain JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (HLA-B7 Antigen)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
EIN - Transplantation. 2007 Aug 27;84(4):561. Mendicino, Michael [added]
MH  - Animals
MH  - Crosses, Genetic
MH  - Female
MH  - Flow Cytometry
MH  - HLA-B7 Antigen/*genetics/*immunology
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Models, Animal
MH  - Spleen/immunology
MH  - Transplantation Tolerance/*immunology
MH  - Transplantation, Heterologous/*immunology
EDAT- 2004/09/24 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/09/24 05:00
PHST- 2004/09/24 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/09/24 05:00 [entrez]
AID - 00007890-200409270-00009 [pii]
AID - 10.1097/01.tp.0000136965.22023.60 [doi]
PST - ppublish
SO  - Transplantation. 2004 Sep 27;78(6):844-52. doi: 
      10.1097/01.tp.0000136965.22023.60.