Functional Divergence among CD103⁺Dendritic Cell Subpopulations following Pulmonary Poxvirus Infection

Abstract

A large number of dendritic cell (DC) subsets have now been identified based on the expression of a distinct array of surface markers as well as differences in functional capabilities. More recently, the concept of unique subsets has been extended to the lung, although the functional capabilities of these subsets are only beginning to be explored. Of particular interest are respiratory DCs that express CD103. These cells line the airway and act as sentinels for pathogens that enter the lung, migrating to the draining lymph node, where they add to the already complex array of DC subsets present at this site. Here we assessed the contributions of these individual populations to the generation of a CD8 ؉ T-cell response following respiratory infection with poxvirus. We found that CD103 ؉ DCs were the most effective antigen-presenting cells (APC) for naive CD8 ؉ T-cell activation. Surprisingly, we found no evidence that lymph node-resident or parenchymal DCs could prime virusspecific cells. The increased efficacy of CD103؉ DCs was associated with the increased presence of viral antigen as well as high levels of maturation markers. Within the CD103 ؉ DCs, we observed a population that expressed CD8␣. Interestingly, cells bearing CD8␣ were less competent for T-cell activation than their CD8␣؊ counterparts. These data show that lung-migrating CD103 ؉ DCs are the major contributors to CD8 ؉ T-cell activation following poxvirus infection. However, the functional capabilities of cells within this population differ with the expression of CD8, suggesting that CD103 ؉ cells may be divided further into distinct subsets.

Cutting Edge: Protective Effect of CX3CR1+ Dendritic Cells in a Vaccinia Virus Pulmonary Infection Model

“…In contrast, recipients of CX3CR1 +/+ NK cells showed no protective response. As professional APCs, DCs are the key instigators of the adaptive immune response (16,17). Our evidence presented in this study shows that expression of CX3CR1 is crucial for DC-mediated protection from a VV lung infection.…”

“…In our model, we observed a reduced VV-specific T cell response in infected CX3CR1 2/2 mice compared with control mice, suggesting that this was at least partly how the DCs exerted their protective influence. In fact, very recently, the lung-migrating CD103 + DC population was implicated as the major contributor to CD8 T cell activation following poxvirus infection (16).…”

“…Total lung RNA was extracted with the Absolutely RNA RT-PCR Miniprep kit (Stratagene), and cDNA was generated with 1 mg RNA, Primer Oligo dT [12][13][14][15][16][17][18] For quantitative RT-PCR, we used the DUAL Labeled Probes and primers from MWG-Biotech and Applied Biosystems TaqMan Master Mix with uracyl-N-glycosylase. We thank Vincent Calvez (Pitié-Salpétrière Hospital, Paris, France) for the RT-PCR assay.…”

Viral infection of the lung: Host response and sequelae

“…59 These results and comparable findings in other models of viral infection suggested that among the DC subsets present in the MLNs, the migrant langerin + CD103 + CD11b − respiratory DCs are the most potent APCs for the activation of naive antiviral T cells after viral lung infection. 65,66 After stimulation by DCs, the now activated naive T cells undergo multiple rounds of cell division in the MLNs and primarily differentiate into antiviral effector T cells. These freshly activated effector T cells emigrate out of the MLNs to the site of infection (ie, the infected lungs), where they can further interact with recently recruited viral antigen-displaying inflammatory DCs.…”

Mycobacterial hypersensitivity pneumonitis requires TLR9–MyD88 in lung CD11b+ CD11c+ cells

“…Surface phenotype of lung CD11c+ cells was analysed for CD11b and CD103 expression as previously described [18][19][20]. After counting, lung CD11c+ cells magnetically purified as described above were stained with FITC-conjugated anti-CD103 (clone M290; BD Biosciences) and phycoerythrin (PE)-conjugated anti-CD11b antibody (clone M1/70; BD Biosciences) [21].…”