Conventional DC (cDC) arise from circulating immediate precursors (pre-cDC), and are currently thought to be terminally differentiated. Here we show that cDC are capable of generating progeny that lost all characteristic features of cDC and aquired regulatory properties. Sorted bone marrow pre-cDCs were cultured on a stromal monolayer in the presence or absence of granulocyte-macrophage colony stimulating factor (GM-CSF). In the absence of GM-CSF, pre-cDC derived DCs gave rise to a homogeneous population of CD11clow MHClow cells (DC-regs) on day 8-10 of culture. DC-regs failed to up-regulate major histocompatibility complex class II (MHCII) and co-stimulatory molecules in response to DC maturation stimuli, were poor stimulators in T cell proliferation assays and suppressed T cell proliferation in cultures containing immuno-stimulatory DC. Co-transfer of DC-regs with DCs in vivo did not inhibit proliferation of T cells. These findings reveal the potential of DCs to generate a regulatory DC population with immunosuppressive properties.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33452 |
| Date | 22 November 2012 |
| Creators | Mikhailova, Anastassia |
| Contributors | Cattral, Mark, Gorczynski, Reginald M. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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