May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Blockade of CCR7-Mediated Direct Allorecognition Pathway in High-Risk Corneal Transplantation
Author Affiliations & Notes
  • Y. Jin
    Department of Ophthalmology, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • S. K. Chauhan
    Department of Ophthalmology, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • D. R. Saban
    Department of Ophthalmology, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • R. Dana
    Department of Ophthalmology, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Y. Jin, None; S.K. Chauhan, None; D.R. Saban, None; R. Dana, None.
  • Footnotes
    Support  NIH/NEI Ro1-12963 to R.D.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 439. doi:https://doi.org/
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    • Get Citation

      Y. Jin, S. K. Chauhan, D. R. Saban, R. Dana; Blockade of CCR7-Mediated Direct Allorecognition Pathway in High-Risk Corneal Transplantation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):439. doi: https://doi.org/.

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Abstract

Purpose: : The role of CCR7 in mediating the migration of donor-derived antigen-presenting cells (APCs) to host draining lymph nodes (LN) in corneal transplantation has been established by our previous study. Here, we further investigate the relationship between CCR7-mediated donor APC trafficking and allo-reaction in high-risk (HR) corneal transplantation.

Methods: : Corneal grafts from either CCR7-KO (CCR7-/-) or wild-type (WT) C57Bl/6 mouse group were transplanted onto the neovascularized corneal beds of the BALB/c recipient mice. Total T cells, CD4+CD25- effector T cells (Teffs) and CD4+CD25+ regulatory T cells (Tregs) were isolated from host draining lymph nodes at week 2 post-transplantation using an immunomagnetic sorter. The frequency of directly primed host T cells to corneal alloantigens was measured by the IFN-γ ELISPOT assay. Treg function was tested by in vitro suppression assay. Kaplan-Meier analysis was adopted to evaluate the survival ratio of the grafts from two groups.

Results: : There was no significant difference in the direct responses triggered between the recipients of CCR7-/- and WT grafts, reflected by a slight decrease in the frequency of IFN-γ-producing T cells in the CCR7-/- group. The frequency of IFN-γ-producing Teffs from CCR7-/- group was 2-fold decreased as compared to that in WT group. However, the inhibitory effects of Tregs from CCR7-/- group were lower than those from WT group, reflected by a 20% reduction in the suppression of IFN-γ-producing T cells in the ELISPOT assay and 30% less suppression of naïve T cells proliferation in anti-CD3 simulated suppression assay. There was no significant difference in the graft survival ratio between two groups.

Conclusions: : Our data demonstrate that CCR7-mediated donor-derived APC trafficking is important for the induction of host Teff as well as Treg which regulate allo-reaction through two opposite directions: sensitization and tolerance. This may be the main reason for the lack of an effect of CCR7 blockade in HR allograft survival.

Keywords: transplantation • immunomodulation/immunoregulation • cornea: basic science 
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