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

Publication ,  Journal Article
Jin, Y; Chauhan, SK; Saban, DR; Dana, R
Published in: Invest Ophthalmol Vis Sci
February 2010

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.

Duke Scholars

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

February 2010

Volume

51

Issue

2

Start / End Page

816 / 821

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • T-Lymphocytes, Regulatory
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, CCR7
  • RNA, Messenger
  • Ophthalmology & Optometry
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jin, Y., Chauhan, S. K., Saban, D. R., & Dana, R. (2010). Role of CCR7 in facilitating direct allosensitization and regulatory T-cell function in high-risk corneal transplantation. Invest Ophthalmol Vis Sci, 51(2), 816–821. https://doi.org/10.1167/iovs.09-3952
Jin, Yiping, Sunil K. Chauhan, Daniel R. Saban, and Reza Dana. “Role of CCR7 in facilitating direct allosensitization and regulatory T-cell function in high-risk corneal transplantation.Invest Ophthalmol Vis Sci 51, no. 2 (February 2010): 816–21. https://doi.org/10.1167/iovs.09-3952.
Jin Y, Chauhan SK, Saban DR, Dana R. Role of CCR7 in facilitating direct allosensitization and regulatory T-cell function in high-risk corneal transplantation. Invest Ophthalmol Vis Sci. 2010 Feb;51(2):816–21.
Jin, Yiping, et al. “Role of CCR7 in facilitating direct allosensitization and regulatory T-cell function in high-risk corneal transplantation.Invest Ophthalmol Vis Sci, vol. 51, no. 2, Feb. 2010, pp. 816–21. Pubmed, doi:10.1167/iovs.09-3952.
Jin Y, Chauhan SK, Saban DR, Dana R. Role of CCR7 in facilitating direct allosensitization and regulatory T-cell function in high-risk corneal transplantation. Invest Ophthalmol Vis Sci. 2010 Feb;51(2):816–821.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

February 2010

Volume

51

Issue

2

Start / End Page

816 / 821

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • T-Lymphocytes, Regulatory
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, CCR7
  • RNA, Messenger
  • Ophthalmology & Optometry
  • Mice, Inbred C57BL
  • Mice, Inbred BALB C
  • Mice
  • Male