Innate Allorecognition Results in Rapid Accumulation of Monocyte-Derived Dendritic Cells

Abstract

Although the mechanisms governing the innate recognition of pathogen-associated molecular patterns have been well defined, how allogeneic cellular stimuli evoke innate responses remains less so. In this article, we report that upon i.v. transfer (to avoid major iatrogenic interference), allogeneic but not syngeneic leukocytes could induce a rapid (after 1 d) accumulation of host monocyte–derived dendritic cells (moDCs) without any increase in conventional DCs. This occurred in various donor–host strain combinations, did not require MHC mismatch, and could be induced by various donor cell types including B cells, T cells, or NK cells. Using RAG−/−γc−/− and scid γc−/−mice with different MHC, we found that the presence of either donor or host lymphoid cells was required. Alloinduced moDC accumulation was significantly reduced when splenocytes from mice deficient in NK cells by genetic ablation were used as donors. A major component of this moDC accumulation appears to be recruitment. Our findings provide new insights into how the innate and adaptive immune system may interact during allogeneic encounters and thus transplant rejection.

Solid Tumor–Induced Immune Regulation Alters the GvHD/GvT Paradigm after Allogenic Bone Marrow Transplantation

“…3) indicates that alloreactivity is involved. Alloreactivity mediated by innate immune cells has only recently been recognized and is still poorly understood (47)(48)(49). Our experiments seem to indicate that in the case of solid tumor and in the TCD transplant, innate alloreactivity is able to resist tumor-induced immunoregulation and, in addition, seem to be confined to the tumor as no GvHD occurs.…”

Heterogeneity, functional specialization and differentiation of monocyte‐derived dendritic cells

“…Therefore, to avoid the potentially confounding impacts of surgery-associated tissue damage, we recently employed a system involving the enumeration of splenic moDCs after intravenous transfer of freshly isolated allogeneic cells. 56 Using this experimental model, in which external danger signals were minimized, we found that host moDCs accumulated rapidly (within 1 day) following the exposure to alloantigen. This accumulation was mainly associated with recruitment of cells from outside the spleen rather than from differentiation or proliferation of in situ monocytes.…”

“…Unfortunately, although elegant and compelling, a potential contribution of surgery‐induced danger signals could not be fully excluded in this study. Therefore, to avoid the potentially confounding impacts of surgery‐associated tissue damage, we recently employed a system involving the enumeration of splenic moDCs after intravenous transfer of freshly isolated allogeneic cells 56 . Using this experimental model, in which external danger signals were minimized, we found that host moDCs accumulated rapidly (within 1 day) following the exposure to alloantigen.…”

GM-CSF in inflammation

“…Monocytes, macrophages, and DC biology There has been recent debate as to whether GM-CSF can give rise to monocyte-derived DCs (MoDCs) in vivo (Greter et al, 2012;Ko et al, 2014;Louis et al, 2015;Chow et al, 2016;Hamilton et al, 2017), even though GM-CSF, often in combination with IL-4, is widely used to generate in vitro murine and human DC populations from bone marrow precursors and blood monocytes, respectively (Inaba et al, 1992;Suzuki et al, 2004a;Conti and Gessani, 2008;van de Laar et al, 2012). However, cell populations derived by GM-CSF in mouse bone marrow cultures are heterogeneous (Lari et al, 2007;Helft et al, 2015;Na et al, 2016;Rogers et al, 2017;Erlich et al, 2019), and their nomenclature is debated as to whether they should be called DCs or macrophages (Lacey et al, 2012;Hume et al, 2013;Xue et al, 2014;Erlich et al, 2019).…”