Role of T cell recruitment and chemokine-regulated intra-graft T cell motility patterns in corneal allograft rejection

Y. Tan, Midhat H Abdulreda, F. Cruz-Guilloty, N. Cutrufello, A. Shishido, R. E. Martinez, S. Duffort, X. Xia, J. Echegaray-Mendez, Robert B Levy, P. O. Berggren, Victor L Perez Quinones

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Keratoplasty is the primary treatment to cure blindness due to corneal opacification. However, immune-mediated rejection remains the leading cause of keratoplasty failure. Here, we utilize an in vivo imaging approach to monitor, track, and characterize in real-time the recruitment of GFP-labeled allo-specific activated (Bonzo) T cells during corneal allograft rejection. We show that the recruitment of effector T cells to the site of transplantation determined the fate of corneal allografts, and that local intra-graft production of CCL5 and CXCL9/10 regulated motility patterns of effector T cells in situ, and correlated with allograft rejection. We also show that different motility patterns associate with distinct in vivo phenotypes (round, elongated, and ruffled) of graft-infiltrating effector T cells with varying proportions during progression of rejection. The ruffled phenotype was characteristic of activated effectors T cells and predominated during ongoing rejection, which associated with significantly increased T cell dynamics within the allografts. Importantly, CCR5/CXCR3 blockade decreased the motility, size, and number of infiltrating T cells and significantly prolonged allograft survival. Our findings indicate that chemokines produced locally within corneal allografts play an important role in the in situ activation and dynamic behavior of infiltrating effector T cells, and may guide targeted interventions to promote graft survival. The authors show that chemokines produced locally within corneal allografts play an important role in the in situ activation and dynamic behavior of infiltrating effector T cells that may guide antichemokine localized interventions to promote corneal allograft survival after transplantation.

Original languageEnglish
Pages (from-to)1461-1473
Number of pages13
JournalAmerican Journal of Transplantation
Volume13
Issue number6
DOIs
StatePublished - Jun 1 2013

Fingerprint

Chemokines
Cell Movement
Allografts
T-Lymphocytes
Transplants
Corneal Transplantation
Transplantation
Phenotype
Graft Survival
Blindness

Keywords

  • Cell motility
  • chemokines
  • corneal transplantation
  • intravital microscopy
  • rejection
  • T cell

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Role of T cell recruitment and chemokine-regulated intra-graft T cell motility patterns in corneal allograft rejection. / Tan, Y.; Abdulreda, Midhat H; Cruz-Guilloty, F.; Cutrufello, N.; Shishido, A.; Martinez, R. E.; Duffort, S.; Xia, X.; Echegaray-Mendez, J.; Levy, Robert B; Berggren, P. O.; Perez Quinones, Victor L.

In: American Journal of Transplantation, Vol. 13, No. 6, 01.06.2013, p. 1461-1473.

Research output: Contribution to journalArticle

Tan, Y, Abdulreda, MH, Cruz-Guilloty, F, Cutrufello, N, Shishido, A, Martinez, RE, Duffort, S, Xia, X, Echegaray-Mendez, J, Levy, RB, Berggren, PO & Perez Quinones, VL 2013, 'Role of T cell recruitment and chemokine-regulated intra-graft T cell motility patterns in corneal allograft rejection', American Journal of Transplantation, vol. 13, no. 6, pp. 1461-1473. https://doi.org/10.1111/ajt.12228
Tan, Y. ; Abdulreda, Midhat H ; Cruz-Guilloty, F. ; Cutrufello, N. ; Shishido, A. ; Martinez, R. E. ; Duffort, S. ; Xia, X. ; Echegaray-Mendez, J. ; Levy, Robert B ; Berggren, P. O. ; Perez Quinones, Victor L. / Role of T cell recruitment and chemokine-regulated intra-graft T cell motility patterns in corneal allograft rejection. In: American Journal of Transplantation. 2013 ; Vol. 13, No. 6. pp. 1461-1473.
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AU - Cutrufello, N.

AU - Shishido, A.

AU - Martinez, R. E.

AU - Duffort, S.

AU - Xia, X.

AU - Echegaray-Mendez, J.

AU - Levy, Robert B

AU - Berggren, P. O.

AU - Perez Quinones, Victor L

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AB - Keratoplasty is the primary treatment to cure blindness due to corneal opacification. However, immune-mediated rejection remains the leading cause of keratoplasty failure. Here, we utilize an in vivo imaging approach to monitor, track, and characterize in real-time the recruitment of GFP-labeled allo-specific activated (Bonzo) T cells during corneal allograft rejection. We show that the recruitment of effector T cells to the site of transplantation determined the fate of corneal allografts, and that local intra-graft production of CCL5 and CXCL9/10 regulated motility patterns of effector T cells in situ, and correlated with allograft rejection. We also show that different motility patterns associate with distinct in vivo phenotypes (round, elongated, and ruffled) of graft-infiltrating effector T cells with varying proportions during progression of rejection. The ruffled phenotype was characteristic of activated effectors T cells and predominated during ongoing rejection, which associated with significantly increased T cell dynamics within the allografts. Importantly, CCR5/CXCR3 blockade decreased the motility, size, and number of infiltrating T cells and significantly prolonged allograft survival. Our findings indicate that chemokines produced locally within corneal allografts play an important role in the in situ activation and dynamic behavior of infiltrating effector T cells, and may guide targeted interventions to promote graft survival. The authors show that chemokines produced locally within corneal allografts play an important role in the in situ activation and dynamic behavior of infiltrating effector T cells that may guide antichemokine localized interventions to promote corneal allograft survival after transplantation.

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