Abstract
The identification of the specific DC subsets providing a critical role in presenting influenza antigens to naïve T cell precursors remains contentious and under considerable debate. Here we show that CD8+ T lymphocyte (TCD8+) responses are severely hampered in C57BL/6 mice deficient in the transcription factor Batf3 after intranasal challenge with influenza A virus (IAV). This transcription factor is required for the development of lymph node resident CD8+ and migratory CD103+CD11b− DCs and we found both of these subtypes could efficiently stimulate anti-IAV TCD8+. Using a similar ex vivo approach, many publications on this subject matter excluded a role for resident, non-migratory CD8+ DC. We postulate the differences reported can partially be explained by how DC are phenotyped, namely the use of MHC class II to segregate subtypes. Our results show that resident CD8+ DC upregulate this marker during IAV infection and we advise against its use when isolating DC subtypes.
Highlights
Dendritic cells (DC) are a heterogeneous bone marrow-derived cell population widely accepted as the key initiators of T cell immunity [1]
We previously argued that two specific subtypes, the CD8+ and CD103+CD11b– DC subsets, drive TCD8+ responses during herpes simplex virus skin infection [20]
A recent series of novel studies identified that the transcription factor Batf3 is required for the development of both the splenic CD8+ and dermal CD103+CD11b– DC subset lineages and mice lacking this gene were ideal for testing our hypothesis [15,16]
Summary
Dendritic cells (DC) are a heterogeneous bone marrow-derived cell population widely accepted as the key initiators of T cell immunity [1]. Considerable complexity surrounds understanding the requirement for such heterogeneity along with pinpointing the underlying role each subset has evolved to provide. DC heterogeneity is most apparent in lymph nodes that drain peripheral sites such as the lung, skin and gastrointestinal tract. These lymph nodes are comprised of two major subsets: plasmacytoid DC and myeloid DC, with the latter commonly referred to as conventional or classical DC (cDC) [2]. CDC isolated from the lymph node that drains the lung represent a mixture of lymphoid resident DC, which do not traffic from the periphery, and tissue-derived, ‘‘migratory’’ DC. Lymphoid resident DC subsets can be subdivided into CD8aexpressing DC (CD8+ DC) and CD82 DC [3,4]. Two defined migratory DC subsets exist and are subcategorized based on their differential expression of the mucosal aE integrin marker CD103 and myeloid marker CD11b (CD103+CD11b2 DC and CD1032CD11b+ DC) [5]
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