Multiple dendritic cell populations activate CD4⁺ T cells after viral stimulation

Dendritic cells (DC) are a heterogeneous cell population that bridge the innate and adaptive immune systems. CD8α DC play a prominent and sometimes exclusive, role in driving amplification of CD8⁺ T cells during a viral infection. Whether this reliance on a single subset of DC also applies for CD4⁺ T cell activation is unknown. We used a direct ex vivo antigen presentation assay to probe the capacity of flow cytometrically purified DC populations to drive amplification of CD4⁺ and CD8⁺ T cells following infection with influenza virus by different routes. This study examined the contributions of non-CD82^a DC populations in the amplification of CD8⁺ and CD4⁺ T cells in cutaneous and systemic influenza viral infections. We confirmed that in vivo, effective immune responses for CD8⁺ T cells are dominated by presentation of antiger by CD8α DC but can involve non-CD8^a DC. In contrast, CD4⁺ T cell responses relied more heavily on the contributions of dermal DC migrating from peripheral lymphoid tissues following cutaneous infection, and CD4 DC in the spleen after systemic infection. CD4⁺ T cell priming by DC subsets that is dependent upon the route of administration raises the possibility that vaccination approaches could be tailored to prime helper T cell immunity. Copyright: