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Published on: April 18, 2016
Dendritic cell-T cell interactions: CD8 alpha alpha expressed on dendritic cells regulates T cell proliferation
Li Hong1, Tonya J Webb, David S Wilkes
1Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, USA.
Insights
CD8alpha expression on dendritic cells (DCs) influences T cell activation. CD8alpha(+) DCs, unlike CD8alpha(-) DCs, showed enhanced T cell proliferation and IL-12 production, suggesting a functional role beyond a simple marker.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD8alpha expression distinguishes lymphoid (CD8alpha(+)) from myeloid (CD8alpha(-)) dendritic cells (DCs).
- Previous studies noted differential T cell proliferation stimulation by CD8alpha(+) and CD8alpha(-) DCs, but the specific function of DC-derived CD8alpha remained unclear.
Purpose of the Study:
- To investigate the hypothesis that CD8alpha expression on DCs regulates DC-induced T cell activation.
- To explore the functional role of CD8alpha in dendritic cell-mediated immune responses.
Main Methods:
- Transduction of bone marrow-derived DCs to express CD8alpha.
- Co-culture experiments with T cells to assess proliferation and cytokine production (IL-12).
- Detection and co-precipitation analysis of LCK kinase in splenic DCs.
Main Results:
- CD8alpha(-) DCs engineered to express CD8alpha showed enhanced T cell proliferation stimulation.
- Engineered CD8alpha(-) DCs produced significantly higher levels of IL-12 when co-cultured with T cells.
- LCK kinase, typically T cell-restricted, was detected in CD8alpha(+) DCs and co-precipitated with CD8alpha, suggesting a signaling role.
Conclusions:
- CD8alpha on dendritic cells is not merely a lineage or maturation marker.
- CD8alpha expression contributes to the functional capacity of DCs in T cell activation and cytokine production.
- The interaction of LCK with CD8alpha in DCs may mediate T cell activation.
Abstract:
Expression of the CD8 alpha alpha homodimer has been used to differentiate lymphoid (CD8alpha(+)) from myeloid (CD8alpha(-)) dendritic cells (DCs). We have reported that CD8alpha(+) and CD8alpha(-) DCs have differential abilities to stimulate proliferation in allogeneic T cells. However, no specific function has been attributed to DC-derived CD8alpha. The current study examines the hypothesis that CD8 alpha alpha expression on DCs regulates DC-induced T cell activation. CD8alpha(-) transduced bone marrow-derived DCs were more potent stimulators of T cell proliferation, and produced significantly greater quantities of IL-12 in co-culture with T cells. LCK, a kinase whose expression is reported to be T cell-restricted and known to bind to the cytoplasmic tail of CD8 alpha beta in T cells, was detected readily in primary CD8alpha(+) splenic DCs and at greater levels than CD8alpha(-) DCs from the same tissues. LCK also co-precipitated with CD8alpha on immunblots strongly suggesting its role in CD8alpha(+) DC-induced T cell activation. Collectively, these data show that CD8alpha expressed on DC may not only be a lineage/maturation marker but also contribute to DC function.
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