ArticleInvestigative ophthalmology & visual science2011
Engagement of TLR2 reverses the suppressor function of conjunctiva CD4+CD25+ regulatory T cells and promotes herpes simplex virus epitope-specific CD4+CD25- effector T cell responses.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- The Path Towards Effective Long-Lasting Tissue-Targeted Prime/Pull/Keep Herpes Simplex Therapeutic Vaccines.Vaccines · 2025Review
- TLR1/2 ligand enhances antitumor efficacy of CTLA-4 blockade by increasing intratumoral Treg depletion.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Age-related Defects in Ocular and Nasal Mucosal Immune System and the Immunopathology of Dry Eye Disease.Ocular immunology and inflammation · 2016Review
- Functional Mechanisms of Treg in the Context of HIV Infection and the Janus Face of Immune Suppression.Frontiers in immunology · 2016Review
- Article
- Cutaneous RANK-RANKL Signaling Upregulates CD8-Mediated Antiviral Immunity during Herpes simplex Virus Infection by Preventing Virus-Induced Langerhans Cell Apoptosis.The Journal of investigative dermatology · 2015Article
- Article
- HIV-1 infection impairs regulatory T-cell suppressive capacity on a per-cell basis.The Journal of infectious diseases · 2014Article
- Prophylactic and therapeutic modulation of innate and adaptive immunity against mucosal infection of herpes simplex virus.Immune network · 2014Review
- Toll-Like Receptor Activation in Immunity vs. Tolerance in Autoimmune Diabetes.Frontiers in immunology · 2014Review
- Protective effects of red ginseng extract against vaginal herpes simplex virus infection.Journal of ginseng research · 2013Article
- Signaling via TLR2 and TLR4 Directly Down-Regulates T Cell Effector Functions: The Regulatory Face of Danger Signals.Frontiers in immunology · 2013Article
- Sex-specific signaling through Toll-Like Receptors 2 and 4 contributes to survival outcome of Coxsackievirus B3 infection in C57Bl/6 mice.Biology of sex differences · 2012Article
- Retinal Muller glia initiate innate response to infectious stimuli via toll-like receptor signaling.PloS one · 2012Article
- Towards a rational design of an asymptomatic clinical herpes vaccine: the old, the new, and the unknown.Clinical & developmental immunology · 2012Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
PURPOSE. The authors recently reported that Foxp3(+)CD4(+) CD25(+(Bright)) "natural" regulatory T cells (nT(reg) cells) are abundant in rabbit conjunctiva and suppress herpes simplex virus (HSV)-1-specific CD4(+) and CD8(+) effector T cells (T(eff) cells). However, little is known about the overall regulatory mechanisms of these nT(reg) cells. The authors investigate the regulation of conjunctiva-resident nT(reg) cells through Toll-like receptors (TLRs) and their effect on ocular mucosal T(eff) cell immunity. METHODS. CD4(+)CD25(+) nT(reg) cells were purified from naive rabbit conjunctivas, and their TLR expression profile was determined. The effects of TLR engagement on nT(reg) cell-mediated suppression of CD4(+) T(eff) cells were determined in vitro and in vivo. RESULTS. The authors found that conjunctiva-resident nT(reg) cells express high levels of TLR2 and TLR9; exposure to the TLR2 ligand lipoteichoic acid (LTA) led to the increased activation and proliferation of nT(reg) cells, and the addition of autologous APCs further increased nT(reg) cell expansion; in contrast, the TLR9 ligand CpG(2007) inhibited the proliferation of nT(reg) cells, and the addition of autologous APCs had no effect on such inhibition; nT(reg) cells treated with LTA, but not with CpG(2007), expressed IFN-γ and IL-10 mRNA, but not TGF-β; consistent with in vitro data, rabbits immunized by topical ocular drops of HSV-gD peptides + TLR2 ligand (LTA) displayed enhanced CD4(+)CD25(-) T(eff) cell immune responses when compared with HSV-gD peptides + TLR9 ligand (CpG(2007)). CONCLUSIONS. Although conjunctiva-resident CD4(+)CD25(+) nT(reg) cells express high level of TLR2 and TLR9, their suppressive function is more significantly reversed after the administration of TLR2 ligand (LTA; P < 0.005) than of TLR9 ligand (CpG(200); P > 0.005). These findings will likely help optimize the topical ocular administration of immunotherapies.
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