Abstract
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-CD8α 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 antigen by CD8α DC but can involve non-CD8α 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.
Highlights
Murine dendritic cells (DC) can be divided into at least six different subsets [1]
DC play minor roles in presentation Subcutaneous inoculation with influenza WSN-gB virus resulted in maximal expansion of endogenous glycoprotein B-specific CD8+ T cells at five days after infection in the popliteal lymph nodes (Figure 1A) and seven days post-infection in the spleen (Figure 1B)
To examine more closely whether the migratory subsets of DC could be involved in the presentation of antigen to CD8+ T cells, later in infection when Langerhans cells may have had an opportunity to migrate to the draining lymph nodes [15], we extended our analysis to include these DC subsets at 48 and 72 h after infection (Figure 3C,D)
Summary
Murine dendritic cells (DC) can be divided into at least six different subsets [1]. Despite this heterogeneity, in previous studies we have established that the tissue-derived CD8a+ (CD8a) DC are the main subset driving CD8+ T cell amplification during the early phase of the immune response [2,3,4,5].In skin infection, migratory DC (such as Langerhans cells and dermal DC) have long been thought to be key mediators of T cell immunity. Even in skin infection with Herpes simplex virus-1 (HSV-1), which does not apparently invoke migratory Langerhans cells directly for immune activation, interplay between these DC transporting antigens and lymph node-resident DC is key to triggering T cell amplification by crosspresentation [6,7]. These findings suggest a more complex view of viral antigen presentation than first thought. They allude to a more likely scenario whereby co-operation between multiple specialised DC is required to prime naıve T cells
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