Purchase this article with an account.
D. J. Carr, C. D. Conrady; Reduction in Dendritic Cell Expression of PDL1 Increases Viral Titer in the Cornea and Associated Decrease in Virus-Specific Cytotoxic T Cells in the Mandibular Lymph Nodes Following Ocular HSV-1 Infection. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5781.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine the relationship between dendritic cell expression of programmed death ligand (PDL)1 and the host innate and adaptive immune response to ocular HSV-1 infection
C57BL/6 mice were administered 200 µg of anti-PDL1 or isotypic control IgG intraperitoneally at day 2, 4, and 6 post infection (pi) following HSV-1 (1,000 plaque forming units/cornea, strain McKrae) infection. Mice were exsanguinated at day 7 pi and the corneas, draining (mandibular) lymph nodes (MLN), and trigeminal ganglia (TG) were removed and assayed for virus titer by plaque assay and leukocyte content by flow cytometry. Analysis of cell subpopulations in the cornea, MLN, and TG by flow included NK cells (NK1.1+CD3-), CD4+ T cells (CD3+CD4+), CD8+ T cells, conventional dendritic cells (DCs, CD11c+B220- and CD11c+B220+), HSV-specific cytotoxic T cells (CTL, CD8+gB495-505 tetramer+), macrophages (F4/80+Gr1-), and neutrophils (F4/80-Gr1+). In addition, PDL1, PDL2, and CD80 expression on DCs and PD1 on T cells was also assessed by flow cytometry.
HSV-1-infected mice treated with anti-PDL1 antibody possessed significantly more virus in the cornea and TG at day 7 pi. Whereas there was no significant change in the infiltration of leukocyte populations in the cornea pi, there was a reduction in CD8+ T cells and HSV-specific CTLs residing in the MLN of anti-PDL1 antibody-treated mice corresponding with a reduction in DCs expressing the co-stimulatory molecule, CD80. PDL1 expression by MLN DCs from anti-PDL1 antibody-treated mice was nearly absent in comparison to isotypic control-treated animals whereas there was a 2-fold increase in PDL2 expression on these cells from the anti-PDL1 antibody-treated group. Consistent with a reduction in HSV-specific CTLs in the MLN of anti-PDL1 antibody-treated mice, there was a significant reduction in the HSV-specific CTLs found in the TG of anti-PDL1 antibody treated mice.
Expression of PDL1 and PDL2 likely maintain a balance between inflammatory and suppressive/regulatory T cells within the MLN and peripherally-infected tissue following HSV-1 infection. Currently, we speculate the relationship is non-redundant with CD11c expression of PDL2 favoring a suppressive environment whereas PDL1 less so. Future studies are necessary to compare PDL1 to PDL2 neutralization as well as PDL1 and PDL2 neutralization as it relates to the inflammatory response and ability of the host to control HSV-1 replication, spread, and establishment of latency.
This PDF is available to Subscribers Only