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Meghan Carr, Hem Raj Gurung, Daniel J Carr; Disruption of Lymphatic Vessel Genesis in the Cornea Suppresses the Development of the Adaptive T Cell Immune Response in the Draining Lymph Node Following HSV-1 Infection. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1852.
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To determine the role of corneal lymphatics in the localized adaptive immune response to ocular HSV-1 infection.
VEGF-A floxed C57BL/6 mice were infected with 200 pfu/cornea of HSV-1, either parental (SC16) or Cre-expressing (SC16 ICP0-Cre). At times post infection (pi) mice were exsanguinated and the cornea was removed and assessed for viral titer and leukocyte subpopulations by plaque assay and flow cytometry, respectively. In addition, the draining (mandibular) lymph nodes (MLN) were investigated for immune, blood endothelial (BEC), and lymphatic endothelial (LEC) cell content as well as blood lymphatic (LYVE-1+) vessel structures by flow cytometry and confocal imaging respectively. <br />
Previously, we reported VEGF-A floxed mice infected with Cre-expressing HSV-1 displayed a significant loss in corneal lymphatic vessel development by day 7 pi through day 30 pi. In the current study, we report no differences in the viral load or number of myeloid-derived or NK cell numbers residing in the cornea at day 7 pi. In contrast, there was a significant loss of CD8 T cells and a trend toward fewer CD4+ T cells in the cornea of the SC16 ICP0-Cre infected VEGF-A floxed mice. More pronounced differences correlative with that found in the cornea were observed in the MLN including a dramatic loss of HSV-specific CD8+ T cells. By day 14 pi, there was a reduction in T lymphocytes residing in the cornea of the SC16 ICP0-Cre infected VEGF-A floxed mice consistent with a loss of T cells but not B cells in the MLN at this time point. Changes in the dynamics of T lymphocyte expansion in the MLN of the SC16 ICP0-Cre infected VEGF-A floxed mice was associated with a significant loss of BEC and LEC numbers as well as lymphatic vessel structure in the MLN.<br />
These results suggest corneal lymphatic vessels and/or local VEGF A expression contributes to the development of the adaptive T cell response to ocular HSV-1 infection.<br />
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