CD31 Expression Defines Heterogeneity of Donor Plasmacytoid Dendritic Cell Populations That Home to the Thymus: Implications for Control of GvHD

Introduction: Plasmacytoid dendritic cells (pDC) are known to possess tolerogenic properties in allogeneic bone marrow transplantation (allo-BMT), but the relationship between pDC lineage and their modulation of graft-versus-host disease (GvHD) has not been defined. Recently, we have shown that murine treatment with the pleiotropic cytokine FMS-like Tyrosine Kinase 3 Ligand (Flt3L) increases pDC content in the marrow, and that allo-BMT of Flt3L-treated marrow (FBM) grafts leads to higher overall survival and reduced GvHD in lethally irradiated hosts. Furthermore, FBM pDC have increased potency in preventing GvHD on a cell-by-cell basis (Hassan, EBMT, 2018). Interestingly, FBM pDC expressed CD11b, a myeloid-specific marker that is not expressed on currently defined pDC. Lineage ontogeny of pDC can be tracked based upon exclusive expression of CD31 and Ly6C on myeloid-progenitor derived pDC, while pDC from lymphoid progenitors express RAG1 and Siglec H. We hypothesized that treatment of murine bone marrow donors with Flt3L, which enhances their GvHD-reducing activity, modifies the distribution of lineage-specific precursors of pDC in bone marrow, and that lineage-associated pDC will have distinct biological activity in allo-BMT.