June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
STAT3/SOCS3 axis modulates CD8-mediated host immunity against HSV-1
Author Affiliations & Notes
  • Fatemeh Navid
    Laboratory of Immunology, NEI, Bethesda, MD
  • Chengrong Yu
    Laboratory of Immunology, NEI, Bethesda, MD
  • Ivy Dambuza
    Laboratory of Immunology, NEI, Bethesda, MD
  • Gregory M. Frank
    Cellular Biology Section, NIAID, Bethesda, MD
  • Charles E. Egwuagu
    Laboratory of Immunology, NEI, Bethesda, MD
  • Footnotes
    Commercial Relationships Fatemeh Navid, None; Chengrong Yu, None; Ivy Dambuza, None; Gregory M. Frank, None; Charles E. Egwuagu, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5989. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Fatemeh Navid, Chengrong Yu, Ivy Dambuza, Gregory M. Frank, Charles E. Egwuagu, Immunology; STAT3/SOCS3 axis modulates CD8-mediated host immunity against HSV-1. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5989.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: Herpes Simplex Virus (HSV-1) is the most common cause of cornea-derived blindness in developed nations and is a major global public health problem. Cytokines have profound influence on the activation, development and expansion of T cells that confer protection against HSV-1 and other infectious agents. The JAK/STAT pathway regulates the intensity and duration of cytokine signals and is in turn under feedback regulation by suppressors of cytokine signaling (SOCS) proteins. Recent reports indicate that STAT3 inhibits T-helper cell proliferation and IL-2 production while SOCS3 inhibits Treg proliferation and suppressive functions. In this study we investigated whether STAT3 and SOCS3 contribute to the regulation of cell-mediated immunity against HSV-1 infection.

Methods: We have generated mice with conditional deletion of STAT3 (STAT3KO) or SOCS3 (SOCS3KO) in CD4 and CD8 T cells and infected them by intraperitoneal injection with the HSV-1 strain REpICP0-EGFP (Journal of Virology, 79:10339-10347, 2005). Viremia was measured at different time points post immunization (p.i.) by plaque assay. Splenocytes and lymph node cells were analyzed for the expansion of HSV-1-specific CD8 cells using an anti HSV-1 gB Tetramer-PE antibody and [3H] Thymidine incorpoaration assay. T cell immunophenotype was characterized by FACS analysis and cytokine secretion was analyzed by the intracellular cytokine assay.

Results: In comparison to WT mice, HSV-1-specific CD8 T cells were significantly elevated in STAT3KO mice at the peak of the infection while loss of SOCS3 in T cells correlated with substantial decrease in HSV-1-specific CD8 T cell numbers in the SOCS3KO mice.

Conclusions: Our data indicate that STAT3 and SOCS3 may have diametrically opposite effects on cell-mediated immune response to HSV-1 infection, with STAT3 inhibiting the expansion of HSV-1-specific CD8 T cells. As SOCS3 antagonizes Treg expansion and suppressive activities, our data suggests that it may promote the expansion of HSV-1-specific CD8 cells by restraining the inhibitory effects of Tregs. Taken together, targeting STAT3/SOCS3 axis might be a beneficial therapeutic strategy to modulate the CD8-mediated host immunity against HSV-1.

Keywords: 545 herpes simplex virus • 555 immunomodulation/immunoregulation • 714 signal transduction  
×
×

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.

×