July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Age-associated changes in T effector and regulatory T cells
Author Affiliations & Notes
  • Cintia S De Paiva
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Humberto Hernandez
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Rodrigo G. de Souza
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Zhiyuan Yu
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Fang Bian
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Cintia De Paiva, Immuneyez (F); Humberto Hernandez, None; Rodrigo de Souza, None; Zhiyuan Yu, None; Fang Bian, None
  • Footnotes
    Support  NIH/NEI EY026893 (CSDP), NEI Training Grant in Vision Sciences T32 EY007001-41 (HH), NIH EY-002520 (Core Grant for Vision Research Department of Ophthalmology), NIH Training Grant T32-AI053831 (FB), Biology of Inflammation Center (CSDP), Research to Prevent Blindness (Dept. of Ophthalmology), The Oshman Foundation, William Stamps Farish Fund, The Hamill Foundation, The Sid Richardson Foundation, and by Baylor Cytometry and Cell Sorting Core (NIH NIAID P30AI036211, NCI P30CA125123, and NCRR S10RR024574).
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 271. doi:
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    • Get Citation

      Cintia S De Paiva, Humberto Hernandez, Rodrigo G. de Souza, Zhiyuan Yu, Fang Bian; Age-associated changes in T effector and regulatory T cells. Invest. Ophthalmol. Vis. Sci. 2019;60(9):271.

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

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Abstract

Purpose : Aging is one of the most recognized risk factors for dry eye disease. The purpose of this study was to investigate the T helper (Th) subtypes and regulatory T cells in C57BL/6J mice, which spontaneously develop dry eye with aging.

Methods : Young (eight-week-old) and aged (24-months old) C57BL/6J female mice were used. The frequency of CD4+IL-17+ (Th17), CD4+IFN-γ+ (Th1) and CD4+Foxp3+ cells were investigated in lacrimal glands (LG) and cervical lymph nodes (CLN) using flow cytometry. Amnis ImageStreamer cytometer confirmed cytokine production. Young and aged CD4+CD25+ and CD4+CD25- cells were isolated from CLNs and spleens as surrogates for regulatory T cells (Tregs) and T responders (Tresps), respectively. These cells were used in mixed lymphocyte reactions and gene expression analysis. Proliferation and production of IFN-γ in culture supernatants was used as endpoints in mixed lymphocyte reactions.

Results : Aged mice had increased frequency of Th1 cells in LG (P<0.05) and CLNs (P<0.01), while Th17 cells increased only in CLNs (P<0.05). There was an increased frequency of CD4+Foxp3+ cells in LGs (P<0.05), CLN (P<0.01), in aged compared to the young group. Elevated CD4+IFN-γ+Foxp3+ cells (LG [P<0.05], CLN [P<0.001]), and CD4+IL-17+Foxp3+ (CLN, P<0.05) were observed in aged mice compared to the young group. Production of IFN-γ by Foxp3+ cells was confirmed by imaging cytometry in LGs and CLNs. Mixed lymphocyte reactions showed that aged Tregs had decreased suppressive ability in young Tresps compared to young Tregs; however, young Tregs failed to suppress proliferation from aged Tresps. Similar results were observed in IFN-γ protein concentration in supernatants. A significant increase in IFN-γ (9 fold), IL-4 (3 fold) and IL-17 (6.83 fold) mRNA was seen in aged Tresps compared to young Tresps. Aged Tregs expressed higher levels of IFN-γ (4.86 fold), IL-17 (14.37 fold) than young Tregs, but still expressed significantly higher levels of IL-10 (12 fold), CTLA-4 (9 fold) and ICOS (2.9 fold) mRNA transcripts than young Tregs (all P<0.001). Median fluorescence intensity of Foxp3 was maintained in LG and CLNs demonstrating that these cells are not “ex-Foxp3+ cells.”

Conclusions : Aging was accompanied by increased frequency of Th1 cells in periocular tissues.Our results show that aging is associated with dysregulation of both T effectors and T regulatory cells. These findings shed light on the pathogenesis of age-related dry eye.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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