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KMID : 0923620100100020046
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Immune Network
2010 Volume.10 No. 2 p.46 ~ p.54
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Roles of Host Nonhematopoietic Cells in Autoimmunity and Donor Cell Engraftment in Graft-versus-host Disease
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Kim Ju-Yang
Cho Hong-Rae
Park So-Hye
Kim Hyun-A
Jung Dae-Hee
Kim Hyun-Ju
Choi Hye-Jeong
Kwon Byung-Suk
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Abstract
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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-2b) or DBA/2 (H-2d)→unirradiated (C57BL/6×DBA/2) F1(BDF1; H-2b/d) murine model of acute GVHD (aGVHD) or chronic GVHD (cGVHD).
Methods: We generated (BDF1→C57BL/6), (BDF1→DBA/2), and (BDF1→BDF1) 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. [Immune Network 2010;10(2):46-54]
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KEYWORD
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Autoimmunity, Chimera, Graft-versus-host disease, Immune tolerance
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