Role of CCR7 in facilitating direct allosensitization and regulatory T-cell function in high-risk corneal transplantation.

Journal Article

PURPOSE: Chemokine receptor 7 (CCR7) is a key homing molecule for immune cell trafficking, including corneal antigen-presenting cell (APC) migration from the inflamed cornea to draining lymph nodes (LNs). Here, the authors investigated the effect of CCR7-facilitated donor APC trafficking on allosensitization, regulatory T-cell (Treg) function, and graft survival in corneal transplantation. METHODS: CCR7(-/-) or wild-type (WT) allogeneic corneal grafts were transplanted onto the neovascularized high-risk recipient beds. Two weeks later, the frequency of directly alloprimed host T cells was measured by the IFN-gamma ELISPOT assay. Treg function was tested by a coculture suppression assay and an IFN-gamma ELISPOT assay. Kaplan-Meier analysis was performed to evaluate graft survival. RESULTS: The recipients of CCR7(-/-) grafts had fewer migrated donor APCs and lower frequency of IFN-gamma-producing T cells in the draining LNs. However, there was no statistically significant difference in transplant survival between recipients of CCR7(-/-) and those of WT grafts. Tregs from the CCR7(-/-) graft recipient group showed reduced regulatory potential for the suppression of proliferation of naive T cells and direct alloprimed T cells and expressed lower Foxp3 levels. In vitro studies confirmed that mature CCR7(+) major histocompatibility complex class II(+) CD86(+) graft-derived dendritic cells were critical for Treg function. CONCLUSIONS: Not only is CCR7-mediated donor-derived APC trafficking to the draining LNs important in the initiation of host T-cell priming, it is crucial for Treg-mediated tolerance.

Full Text

Duke Authors

Cited Authors

  • Jin, Y; Chauhan, SK; Saban, DR; Dana, R

Published Date

  • February 2010

Published In

Volume / Issue

  • 51 / 2

Start / End Page

  • 816 - 821

PubMed ID

  • 19797201

Electronic International Standard Serial Number (EISSN)

  • 1552-5783

Digital Object Identifier (DOI)

  • 10.1167/iovs.09-3952

Language

  • eng

Conference Location

  • United States