Abstract
BackgroundAt present, it is highly controversial whether pure mast cells can serve as antigen presenting cells, and it is not known whether the capacity of antigen presenting function is temporally restricted to a particular subset of differentiated mast cells. Evidence is presented for a novel surface FcεRIhi , MHC II +, and c-kit + pure mast cell subset, temporally restricted as antigen-presenting cells in the immune axis of T-cell activation.ResultsBone marrow-derived mast cells (BMMC) cultured in the presence of IL-3 for three weeks are pure mast cells based on surface expression of lineage-specific marker, c-kit and FcεRI. Herein we present the first demonstration that approximately 98.7% c-kit + and FcεRI expressing BMMC, further depleted of any contaminated professional antigen-presenting cells, are still fully capable of presenting antigens, i.e., OVA protein, OVA peptide, and IgE-TNP-OVA, to OVA peptide-specific T-cell hybridomas. Notably, IgE-dependent antigen presentation is more efficient compared to that resulting from direct antigen uptake. Importantly, we present the novel finding that only surface FcεRIhi mast cells, also expressing surface MHC II exhibited antigen-presenting function. In contrast, surface FcεRIlo mast cells without expressing surface MHC II were not capable of antigen presentation. Interestingly, the antigen-presenting function of BMMC was irrevocably lost during the third and fourth week in IL-3 or SCF containing cultures.ConclusionsThis is the first observation to attribute a spatiotemporally restricted antigen-presenting function to a subset of three-week old pure BMMC expressing both high levels of surface FcεRI and surface MHC II. We propose that mast cells play an important role in immune deviating and/or sustaining the activation of infiltrating CD4 T-cells, and modulating T-cell mediated allergic inflammation via its flexibility to present antigens and antigen-IgE complexes.
Highlights
At present, it is highly controversial whether pure mast cells can serve as antigen presenting cells, and it is not known whether the capacity of antigen presenting function is temporally restricted to a particular subset of differentiated mast cells
Pure bone marrowderived mast cells (BMMC) depleted of professional antigenpresenting cells (APC) present antigens and are more efficient via Type I high affinity IgE Fc receptor (FcεRI)-mediated antigen uptake BMMC cultured in IL-3 for three weeks were shown to present antigen (9)
It was previously reported that a minor subset of FcεRI + mast cells, exhibiting surface c-kit, exists in IL-3/stem cell factor (SCF) containing bone marrow cultures [16]
Summary
It is highly controversial whether pure mast cells can serve as antigen presenting cells, and it is not known whether the capacity of antigen presenting function is temporally restricted to a particular subset of differentiated mast cells. Evidence is presented for a novel surface FcεRIhi , MHC II +, and c-kit + pure mast cell subset, temporally restricted as antigen-presenting cells in the immune axis of T-cell activation. Mast cells are traditionally thought of as a secretory cell type releasing inflammatory mediators in IgE-dependent inflammation[1,2]. Their role in innate immunity against pathogens has been uncovered, which is associated with their uptake and clearance of the microbes [3,4]. The temporally restricted APC function of BMMC indicates a flexibility of mast cells in playing a role in CD4 T-cell dichotomy and/or sustaining CD4 Tcell activation
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