Roles of Host Nonhematopoietic Cells in Autoimmunity and Donor Cell Engraftment in Graft-versus-host Disease
Immune Network
;
: 46-54, 2010.
Article
in English
| WPRIM
| ID: wpr-164525
ABSTRACT
BACKGROUND:
Graft-versus-host disease (GVHD) is initiated when alloreactive donor T cells are primed by host APCs to undergo clonal expansion and maturation. Since there is a controversy regarding the role of nonhematopoietic cells in GVHD, we wanted to investigate the influence of MHC disparity on nonhematopoietic cells on the pathogenesis of GVHD in the MHC-haplomismatched C57BL/6 (H-2(b)) or DBA/2 (H-2(d))-->unirradiated (C57BL/6xDBA/2) F(1)(BDF(1); H-2(b/d)) murine model of acute GVHD (aGVHD) or chronic GVHD (cGVHD).METHODS:
We generated (BDF(1)-->C57BL/6), (BDF(1)-->DBA/2), and (BDF(1)-->BDF(1)) chimeras and examined GVHD-related parameters and donor cell engraftment in those chimeras.RESULTS:
Using this experimental system, we found that 1) severe aGVHD across MHC Ag barrier depends on the expression of nonhematopoietically rather than hematopoietically derived alloAgs for maximal GVHD manifestations; 2) host APCs were sufficient to break B cell tolerance to self molecules in cGVHD, whereas host APCs were insufficient to induce autoimmunity in aGVHD; 3) donor cell engraftment was greatly enhanced in the host with MHC-matched nonhematopoietic cells.CONCLUSION:
Taken together, our results provide an insight into how MHC disparity on GVHD target organs contribute to the pathogenesis of GVHD.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Tissue Donors
/
T-Lymphocytes
/
Autoimmunity
/
Chimera
/
Graft vs Host Disease
/
Immune Tolerance
Limits:
Humans
Language:
English
Journal:
Immune Network
Year:
2010
Type:
Article
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