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Victor Sendra, Arsia Jamali, Maria Jose Lopez, Pedram Hamrah; Plasmacytoid Dendritic Cells Mediate T cell Responses by Direct Interaction in Lymph Nodes during Herpes Simplex Virus-1 Keratitis. Invest. Ophthalmol. Vis. Sci. 2016;57(12):331.
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© ARVO (1962-2015); The Authors (2016-present)
Plasmacytoid dendritic cells (pDCs), a highly functional subset of immune cells, play a key role in anti-viral responses and link innate and adaptive immune responses through (Toll Like Receptor) TLR 7/9 activation. Here we investigate the presence of activated pDCs in draining lymph nodes (dLNs) and their role in modulating T cell responses in the acute herpes simplex virus (HSV)-1 keratitis
Corneal infection was induced by inoculation of HSV-1 after scarification. Submandibular dLNs were excised and quantified for pDCs by flow cytometry or immunofluorescence staining of cryosections for pDC markers (CD11c, PDCA-1), T cells (CD3) and activation markers (CD86 and MHC-II). Intravital multiphoton microscopy (IV-MPM) was performed in dLNs in Tred mice (T cells are red) after adoptive transfer of pDC-GFP (expression green fluorescence protein) in steady state and after corneal inoculation with TLR9 agonist and HSV-1 to determine the kinetics of pDCs and their interactions with T cells
We observed an increased number of pDCs in dLNs (4-folds, P<0.05) after corneal HSV-1 infection, with an increased percentage of activated pDCs (MHCII+CD86+) (72% vs 42%, P<0.05) and in total T cells (CD45+ CD3+) (2.5 fold, P<0.05) compared to naïve mice. In dLN, pDCs are mainly distributed in the parafollicular cortex (2.9-fold) compared to the follicular, and (1.6-fold) to the subcapsular areas respectively (P<0.05) after corneal HSV-1 infection; similarly in steady state, the distribution is 3.8 fold in the parafollicular area compared to the follicular area (P<0.05). Further, IV-MPM imaging in dLNs from Tred mice showed an increased motility of adoptively transferred pDC after corneal inoculation of TLR9 agonist and HSV-1 with an increased velocity and track length (P<0.001) compared to steady state pDCs (corneal inoculation with PBS). Moreover, around 40% of actively motile pDCs established contact with T cells with durations of >5 minutes demonstrating direct interaction
In dLNs, pDCs are increased during HSK with an increased number of activated pDCs. Also, pDCs are located mainly in the parafollicular cortex where they directly interact with T cells and mediate anti-viral immune responses. This study, for the first time, demonstrates in vivo imaging of submandibular LNs, allowing the study of pDCs and their interaction with T cells in context
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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