May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Th2-Mediated Airway Hyperreactivity Exacerbates Corneal Allograft Rejection
Author Affiliations & Notes
  • J. Y. Niederkorn
    Ophthalmology, University Texas Southwestern Medical Center, Dallas, Texas
  • P. W. Chen
    Ophthalmology, University Texas Southwestern Medical Center, Dallas, Texas
  • C. Stevens
    Ophthalmology, University Texas Southwestern Medical Center, Dallas, Texas
  • J. Mellon
    Ophthalmology, University Texas Southwestern Medical Center, Dallas, Texas
  • E. Mayhew
    Ophthalmology, University Texas Southwestern Medical Center, Dallas, Texas
  • Footnotes
    Commercial Relationships  J.Y. Niederkorn, None; P.W. Chen, None; C. Stevens, None; J. Mellon, None; E. Mayhew, None.
  • Footnotes
    Support  EY007641, EY016664, and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3725. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      J. Y. Niederkorn, P. W. Chen, C. Stevens, J. Mellon, E. Mayhew; Th2-Mediated Airway Hyperreactivity Exacerbates Corneal Allograft Rejection. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3725. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : Previous studies have demonstrated that allergic conjunctivitis increases the incidence and tempo of corneal allograft rejection in mice. We wished to determine if Th2-based allergic inflammation in the lungs or Th1-based inflammation of the skin would exacerbate corneal graft rejection.

Methods: : Airway hyperreactivity (AHR) was induced in BALB/c mice using either ovalbumin (OVA) or short ragweed extract (SRW). AHR was confirmed by plethysmography and by ELISA and histological analysis of bronchoalveolar lavage fluid (BALF). Contact hypersensitivity was induced by skin painting with oxazalone prior to corneal transplantation. Delayed-type hypersensitivity (DTH) responses to donor alloantigens and to skin sensitization were determined using conventional ear-swelling assays. C57BL/6 corneal allografts were transplanted orthotopically to naïve mice, mice sensitized and challenged with oxazalone, or mice with ongoing AHR.

Results: : Mice with ongoing AHR that was induced with SRW displayed a higher incidence and a swifter tempo of corneal allograft rejection compared to mice treated with the alum adjuvant (94% rejection vs. 50% rejection; median survival time [MST] 21 days vs. 50 days; P= 0.007). Likewise, mice with AHR that was induced with OVA displayed a similar exacerbation of corneal allograft rejection (90% rejection vs. 50% rejection; MST = 20 days vs. 56 days; P=0.004). By contrast, mice with ongoing contact hypersensitivity, which is a cutaneous Th1 immune-mediated inflammatory disease, did not reject their corneal allografts at an incidence or a tempo that was significantly different from naïve controls (50% rejection vs. 60% rejection; MST =35 days vs. 38 days; P>0.05). Although allergic inflammatory lesions are characterized by a preponderance of eosinophils, the histopathological features of rejected corneal allografts in mice with AHR, contact hypersensitivity, or vehicle controls were not significantly different and were characterized by a mixed inflammatory infiltrate comprised of lymphocytes and neutrophils.

Conclusions: : Th2-mediated inflammatory diseases are associated with an increased risk for corneal allograft rejection. Allergy-induced exacerbation of corneal allograft rejection is not due to inflammation of the graft bed, but is a systemic alteration of the alloimmune response. Interestingly, ongoing Th1-based inflammation of the skin does not exacerbate corneal allograft rejection. Thus, tilting the systemic immune phenotype to a Th2 pathway exacerbates corneal allograft rejection and does not promote graft survival as previously suspected.

Keywords: transplantation • immunomodulation/immunoregulation • 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.

×