Effect of CXCL-1/KC production in high risk vascularized corneal allografts on T cell recruitment and graft rejection.
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-2b) 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.


CONCLUSIONS
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.
Amescua
Guillermo
G
Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Collings
Fitz
F
Sidani
Amer
A
Bonfield
Tracey L
TL
Rodriguez
Juan P
JP
Galor
Anat
A
Medina
Carlos
C
Yang
Xiaoping
X
Perez
Victor L
VL
D000818:Animals; D054360:Chemokine CXCL1 / Q000235:genetics* / Q000627:therapeutic use; D003315:Cornea / Q000276:immunology; D016039:Corneal Transplantation / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D014184:Transplantation, Homologous / Q000276:immunology
D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse