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Roles of Host Nonhematopoietic Cells in Autoimmunity and Donor Cell Engraftment in Graft-versus-host Disease

  • Kim, Ju-Yang (Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan) ;
  • Park, So-Hye (School of Biological Sciences, University of Ulsan) ;
  • Kim, Hyun-A (School of Biological Sciences, University of Ulsan) ;
  • Jung, Dae-Hee (School of Biological Sciences, University of Ulsan) ;
  • Kim, Hyun-Ju (School of Biological Sciences, University of Ulsan) ;
  • Choi, Hye-Jeong (Department of Pathology, Ulsan University Hospital, School of Medicine, University of Ulsan) ;
  • Cho, Hong-Rae (Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan) ;
  • Kwon, Byung-Suk (Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan)
  • Received : 2010.03.01
  • Accepted : 2010.03.31
  • Published : 2010.04.30
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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 $(H-2^b){\rightarrow}$unirradiated ($C57BL/6{\times}DBA/2$) $F_1(BDF_1;\;H-2^{b/d})$ murine model of acute GVHD (aGVHD) or chronic GVHD (cGVHD). Methods: We generated ($BDF_1{\rightarrow}C57BL/6$), ($BDF_1{\rightarrow}DBA/2$), and ($BDF1{\rightarrow}BDF_1$) 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.

Keywords

References

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