Host dendritic cells alone are sufficient to initiate acute graft-versus-host disease

UA Duffner, Y Maeda, KR Cooke, P Reddy… - The Journal of …, 2004 - journals.aai.org
UA Duffner, Y Maeda, KR Cooke, P Reddy, R Ordemann, C Liu, JLM Ferrara, T Teshima
The Journal of Immunology, 2004journals.aai.org
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 …
Abstract
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.
journals.aai.org