| First Author | Duffner UA | Year | 2004 |
| Journal | J Immunol | Volume | 172 |
| Issue | 12 | Pages | 7393-8 |
| PubMed ID | 15187116 | Mgi Jnum | J:90834 |
| Mgi Id | MGI:3044850 | Doi | 10.4049/jimmunol.172.12.7393 |
| Citation | Duffner UA, et al. (2004) Host dendritic cells alone are sufficient to initiate acute graft-versus-host disease. J Immunol 172(12):7393-8 |
| abstractText | Alloantigen expression on host APCs is essential to initiate graft-vs-host disease (GVHD); however, critical APC subset remains to be elucidated. We compared the ability of dendritic cells (DCs) and B cells to initiate acute GVHD by an add-back study of MHC class II-expressing APCs (II(+/+)) into MHC class II-deficient (II(-/-)) mice that were resistant to CD4-dependent GVHD. Injection of host-derived, but not donor-derived, II(+/+) DCs or host-derived II(+/+) B cells, was sufficient to break GVHD resistance of II(-/-) mice and induced lethal acute GVHD. By contrast, host-derived II(+/+) B cells, both naive and LPS stimulated, failed to induce activation or tolerance of donor CD4(+) T cells. Similarly, in a model of CD8-dependent GVHD across MHC class I mismatch injection of allogeneic DCs, but not B cells, induced robust proliferation of donor CD8(+) T cells and broke GVHD resistance of chimeric recipients in which APCs were syngeneic to donors. These results demonstrate that host-derived DCs are critical in priming donor CD4(+) and CD8(+) T cells to cause GVHD, and selective targeting of host DCs may be a promising strategy to prevent GVHD. |
