Pediatric tolerogenic DCs expressing CD4 and immunoglobulin-like transcript receptor (ILT)-4 secrete IL-10 in response to Fc and adenosine

We characterized a novel population of tolerogenic myeloid dendritic cells (tmDCs) defined as CD11c(+)CD11b(+)CD14(+)CD4(+) and immunoglobulin-like transcript receptor (ILT)-4(+) that are significantly more abundant in the circulation of infants and young children than in adults. TmDCs secrete the immunosuppressive lymphokine interleukin (IL)-10 when stimulated with the heavy constant region of immunoglobulins (Fc) and express high levels of the adenosine A(2A) receptor (A(2A)R), which, when activated by adenosine, inhibits the release of pro-inflammatory cytokines from most immune cells. Here we show that stimulation of the A(2A)R on tmDCs by regadenoson or N-ethylcarboxamidoadenosine (NECA) rapidly increases cyclic AMP accumulation and enhances IL-10 production under Fc stimulatory conditions. In co-culture experiments, tmDCs inhibit the differentiation of naive Tcells to a pro-inflammatory phenotype. In conclusion, although DCs are classically viewed as antigen presenting cells that activate Tcells, we show an independent role of tmDCs in pediatric immune regulation that may be important for suppressing Tcell responses to neoantigens in infants and young children.