TY - JOUR
T1 - Host dendritic cells alone are sufficient to initiate acute graft-versus-host disease
AU - Duffner, Ulrich A.
AU - Maeda, Yoshinobu
AU - Cooke, Kenneth R.
AU - Reddy, Pavan
AU - Ordemann, Rainer
AU - Liu, Chen
AU - Ferrara, James L.M.
AU - Teshima, Takanori
PY - 2004/6/15
Y1 - 2004/6/15
N2 - 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-defficient (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.
AB - 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-defficient (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.
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U2 - 10.4049/jimmunol.172.12.7393
DO - 10.4049/jimmunol.172.12.7393
M3 - Article
C2 - 15187116
AN - SCOPUS:2942627451
SN - 0022-1767
VL - 172
SP - 7393
EP - 7398
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -