April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Regulatory T cell mediated suppression of dendritic cells in a mouse model of dry eye
Author Affiliations & Notes
  • Katherine S Held
    Inflammation R&D, Allergan Inc, Irvine, CA
  • Chris S Schaumburg
    Inflammation R&D, Allergan Inc, Irvine, CA
  • Jianping Gao
    Inflammation R&D, Allergan Inc, Irvine, CA
  • Julio Nieves
    Inflammation R&D, Allergan Inc, Irvine, CA
  • Euikyon Oh
    Inflammation R&D, Allergan Inc, Irvine, CA
  • Larry A Wheeler
    Inflammation R&D, Allergan Inc, Irvine, CA
  • Virginia L Calder
    Genetics, University College London, London, United Kingdom
  • Jerry Y Niederkorn
    Ophthalmology, Univeristy of Texas SW-Med Center, Dallas, TX
  • Stephen C Pflugfelder
    Ophthamology, Baylor College of Medicine, Houston, TX
  • Michael E Stern
    Inflammation R&D, Allergan Inc, Irvine, CA
  • Footnotes
    Commercial Relationships Katherine Held, Allergan, Inc. (E); Chris Schaumburg, Allergan, Inc. (E); Jianping Gao, Allergan, Inc. (E); Julio Nieves, Allergan, Inc. (E); Euikyon Oh, Allergan, Inc. (E); Larry Wheeler, Allergan, Inc. (E); Virginia Calder, Allergan, Inc. (C); Jerry Niederkorn, Allergan, Inc. (C); Stephen Pflugfelder, Allergan, Inc. (C); Michael Stern, Allergan, Inc. (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3653. doi:
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      Katherine S Held, Chris S Schaumburg, Jianping Gao, Julio Nieves, Euikyon Oh, Larry A Wheeler, Virginia L Calder, Jerry Y Niederkorn, Stephen C Pflugfelder, Michael E Stern; Regulatory T cell mediated suppression of dendritic cells in a mouse model of dry eye. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3653.

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

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Purpose: To evaluate the immunosuppressive properties of regulatory T cells, Tregs, against dendritic cell activation following induction of experimental dry eye disease.

Methods: C57Bl/6 wild-type female mice were exposed to desiccating environmental stress (DS; low humidity <40%, constant airflow, and subcutaneous scopolamine dosing) for up to 10 days. Flow cytometry was used to characterize CD4+ Tregs within the cervical lymph nodes and spleen to i.) distinguish the frequencies of inducible and natural regulatory T cells (iTregs and nTregs, respectively) using Helios or Neuropilin-1 as putative markers for thymus-derived nTregs, ii.) evaluate Treg immune suppression of dendritic cell maturation by cell-contact mediated by CTLA4 and LAG3, and by paracrine signaling mediated by IL-10 and TGF-β (LAP) inhibitory cytokines.

Results: The frequencies of CD4+ iTregs and nTregs were significantly increased at day 3 DS (p≤ 0.01), while these populations decreased at day 10 DS, relative to controls. CD4+ iTregs and nTregs showed significantly increased expression of CTLA4 and LAG3 (p<0.001), and increased IL-10 and TGF-β expression at day 3 DS, compared to controls. Co-culture of bone-marrow derived dendritic cells with DS-derived Tregs resulted in a greater dose-dependent decrease in dendritic cell maturation compared to control-derived Tregs. Furthermore, suppression of dendritic cells by Tregs derived from control mice was contact-dependent, while paracrine-mediated inhibition contributed to DS-derived Treg suppression.

Conclusions: These results indicate that iTregs and nTregs increase early in response to desiccating stress and have an increased ability to suppress dendritic cell maturation by paracrine-mediated inhibition.

Keywords: 555 immunomodulation/immunoregulation • 486 cornea: tears/tear film/dry eye • 557 inflammation  

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