CD103+ RDCs drive CD8+ T cell differentiation into lung-homing T effector cells
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CD11bhi RDCs stimulate CD8+ T cell differentiation into central memory-like T effector cells
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CD103+ RDCs express elevated CD24 compared to CD11bhi RDCs
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RDC CD24 modulates CD8+ T cell activation by presenting HMGB1 to T cell RAGE
Summary
The contribution of different DC subsets to effector and memory CD8+ T cell generation during infection and the mechanism by which DCs controls these fate decisions is unclear. Here we demonstrated that the CD103+ and CD11bhi migratory respiratory DC (RDC) subsets after influenza virus infection activated naive virus-specific CD8+ T cells differentially. CD103+ RDCs supported the generation of CD8+ T effector (Teff) cells, which migrate from lymph nodes to the infected lungs. In contrast, migrant CD11bhi RDCs activated CD8+ T cells characteristic of central memory CD8+ T (CD8+ Tcm) cells including retention within the draining lymph nodes. CD103+ RDCs expressed CD24 at an elevated level, contributing to the propensity of this DC subpopulation to support CD8+ Teff cell differentiation. Mechanistically, CD24 was shown to regulate CD8+ T cell activation through HMGB1-mediated engagement of T cell RAGE. Thus, there is distribution of labor among DC subsets in regulating CD8+ T cell differentiation.