Effect of CXCL-1/KC production in high risk vascularized corneal allografts on T cell recruitment and graft rejection

Guillermo Amescua, Fitz Collings, Amer Sidani, Tracey L. Bonfield, Juan P. Rodriguez, Anat Galor, Carlos Medina, Xiaoping Yang, Victor L. Perez

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Background. The survival rate of corneal allografts in high-risk vascularized corneal bed recipients is poor, similar to vascularized solid organ allografts. Although the early induction of selective chemokines in solid organs is required for the optimal recruitment of T cells into rejecting allografts, little is known about the role of these chemokines in high risk corneal allografts. Methods. Orthotopic corneal allotransplants were performed in low-risk (nonvascularized) and high-risk (vascularized) C57BL/6 (H-2 b) recipients using Balb/c (H-2d) donors. Intragraft production of CXC chemokines was measured by Luminex and enzyme-linked immunosorbent assay on corneal transplant extracts at different times after surgery. Rabbit anti-KC serum was used to test its role in high risk corneal allograft survival. Results. Early upregulation of CXCL1/KC occurs 3 days after transplantation in high risk allograft only. Moreover, the T-cell chemoattractants, CXCL9/Mig and CXCL10/IP10, are produced late (day 10) after surgery and their production correlates with the recruitment of CD4 T cells into the graft. Furthermore, in vivo neutralization of CXCL1/KC with anti-KC sera results in increased graft survival and decreased recruitment of T cells into high-risk allografts. Conclusion. We propose that a high risk vascularized cornea behaves like a vascularized solid organ transplant. The early production of CXCL1/KC is crucial to the induction of T-cell chemoattractants necessary for the recruitment of allospecific CD4 T cells into the graft. In vivo neutralization of CXCL1/KC represents a potential novel therapy that could be used to increase the survival rate of high-risk vascularized corneal allografts.

Original languageEnglish (US)
Pages (from-to)615-625
Number of pages11
JournalTransplantation
Volume85
Issue number4
DOIs
StatePublished - Dec 1 2008

Keywords

  • CXCL1/KC
  • High-risk corneal allograft
  • Murine model
  • T-cell chemokines
  • T-cell recruitment

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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