April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
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
Author Affiliations & Notes
  • Anthony B. Nesburn
    Gavin Herbert Eye Institute, University of California, Irvine, Orange, California
  • Gargi Dasgupta
    Gavin Herbert Eye Institute, University of California, Irvine, Orange, California
  • Aziz A. Chentoufi
    Gavin Herbert Eye Institute, University of California, Irvine, Orange, California
  • Payam Falatoonzadeh
    Gavin Herbert Eye Institute, University of California, Irvine, Orange, California
  • Lourie A. Urbano
    Gavin Herbert Eye Institute, University of California, Irvine, Orange, California
  • Ayesha Akhtarmalik
    Gavin Herbert Eye Institute, University of California, Irvine, Orange, California
  • Kimberly Nguyen
    Gavin Herbert Eye Institute, University of California, Irvine, Orange, California
  • Lilit Ablabutyan
    Gavin Herbert Eye Institute, University of California, Irvine, Orange, California
  • Lbachir BenMohamed
    Gavin Herbert Eye Institute, University of California, Irvine, Orange, California
  • Footnotes
    Commercial Relationships  Anthony B. Nesburn, None; Gargi Dasgupta, None; Aziz A. Chentoufi, None; Payam Falatoonzadeh, None; Lourie A. Urbano, None; Ayesha Akhtarmalik, None; Kimberly Nguyen, None; Lilit Ablabutyan, None; Lbachir BenMohamed, None
  • Footnotes
    Support  This work was supported by Public Health Service NIH grants to LBM EY14900 and EY019896, The Discovery Eye Foundation, The Henry L. Guenther Foundation, and Research to Prevent Blindness Challenge gra
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1930. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Anthony B. Nesburn, Gargi Dasgupta, Aziz A. Chentoufi, Payam Falatoonzadeh, Lourie A. Urbano, Ayesha Akhtarmalik, Kimberly Nguyen, Lilit Ablabutyan, Lbachir BenMohamed; 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. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1930.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: : We recently reported that Foxp3+CD4+CD25+(Bright) "natural" regulatory T cells (nTreg cells) are abundant in rabbit conjunctiva and suppress HSV-1-specific CD4+ and CD8+ effector T cells (Teff cells). However, little is known about these nTreg cells and their regulatory mechanisms. This study investigates the regulation of conjunctiva resident nTreg cells through Toll-like receptors (TLRs) and their effect on ocular mucosal Teff cell immunity.

Methods: : CD4+CD25+ nTreg cells were purified from naïve rabbit conjunctivas and their TLR expression profile was determined. The effects of TLRs engagement on nTreg cell-mediated suppression of CD4+ Teff cells were determined in vitro and in vivo.

Results: : We found that: (i) Conjunctiva resident nTreg cells express high levels of TLR2 and TLR9; (ii) Exposure to TLR2 ligand, lipoteichoic acid (LTA), led to increased activation and proliferation of nTreg cells and the addition of autologous APCs further increased nTreg cell expansion; (iii) In contrast, the TLR9 ligand, CpG2007, inhibited the proliferation of nTreg cells, and the addition of autologous APCs had no effect on such inhibition; (iv) nTreg cells treated with LTA, but not with CpG2007, expressed IFN-γ and IL-10 mRNA, but not TGF-β; (v) Consistent with in vitro data, rabbits immunized by topical ocular drops of HSV-gD peptides + TLR2 ligand (LTA), displayed enhanced CD4+CD25- Teff cell immune responses, when compared to HSV-gD peptides + TLR9 ligand (CpG2007).

Conclusions: : Although conjunctiva resident CD4+CD25+ nTreg cells express high level of TLR2 and TLR9, their suppressive function is more significantly reversed following administration of TLR2 ligand (LTA, p <0.005) than TLR9 ligand (CpG200, p >0.005). The findings will likely help optimize the topical ocular administration of immuno-therapies.

Keywords: immunomodulation/immunoregulation • herpes simplex virus • immune tolerance/privilege 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×