Effect of CXCL-1/KC Production in High Risk Vascularized Corneal Allografts on T Cell Recruitment and Graft Rejection

Amescua, Guillermo; Collings, F.; Sidani, Amer; Bonfield, Tracey L.; Rodríguez, Juan Pablo Loyola; Galor, Anat; Medina, Carlos A.; Yang, Xiao‐Ping; Pérez, Víctor L.

doi:10.1097/tp.0b013e3181636d9d

Cited by 34 publications

(33 citation statements)

References 41 publications

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Section: Chemokines and Their Receptors In Acute Gvhdmentioning

confidence: 99%

“…33 They have a direct role as chemoattractants for CXCR2-expressing neutrophils, 60,61 but can also mediate T-cell recruitment through the induction of CXCL9 and CXCL10. 60 Except for the GI tract, CXCL1 expression was strongly increased between week 1 and week 2 after allo-BMT in all target organs (Figure 6a) and correlated with inflammatory cytokine expression (Supplementary Table S5). Upregulation was highest in the liver, followed by the tongue and lung, and whereas expression in the latter two organs as well as in the GI tract did not differ from that of syngeneic controls at later time points, CXCL1 expression remained significantly elevated in the liver throughout the duration of the study and correlated with the severity of hepatic pathology (Supplementary Table S5).…”

Section: Chemokines and Their Receptors In Acute Gvhdmentioning

confidence: 99%

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Chemokine and chemokine receptor expression analysis in target organs of acute graft-versus-host disease

et al. 2009

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Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic bone marrow transplantation (allo-BMT), and infiltration of donor leukocytes into aGVHD target organs is partially orchestrated by chemokines. Using a murine BMT model, the expression of 30 chemokines or chemokine receptors in the lung, liver, gut and tongue was analyzed using real-time PCR at 1, 2, 3 and 6 weeks after BMT during the development of clinical aGVHD and target organ histopathology. CXCL9-11 expression was linked to elevated expression of CXCR3 in the gut, lung and tongue. In contrast, hepatic CXCR3 expression was not changed, whereas a clear association was seen for CXCL16 and CXCR6 expression. An elevated intestinal CCL3 expression 1 week after allo-BMT was associated with an increased expression of CCR5 but not CCR1 or CCR3, and in the lung and liver CCL3-CCL5 expression was associated with increases in CCR1 and CCR5. Overexpression of CCL2, CCL8, CCL12 and their receptor CCR2 was found in the liver and lung, but not in the gut and tongue. On the basis of the differences in kinetics and organ distribution, more studies are required to better characterize specific targets within this network, as this will allow the development of novel preventive and therapeutic approaches by using single or multiple targeting reagents.

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Section: Chemokines and Their Receptors In Acute Gvhdmentioning

confidence: 99%

Section: Chemokines and Their Receptors In Acute Gvhdmentioning

confidence: 99%

Chemokine and chemokine receptor expression analysis in target organs of acute graft-versus-host disease

et al. 2009

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“…A standard scoring system of 0-4 was used for corneal opacification: 0 = clear, 1 = slight haze, 2 = increased haze but anterior chamber structures are visible, 3 = advanced haze with difficult view of anterior chamber structures, and 4 = opaque cornea without view of anterior chamber structures. Grafts that received two consecutive scores $ 3 without resolution were considered rejected (18).…”

Section: Orthotopic Corneal Transplantation and Graft Survival Evaluamentioning

confidence: 99%

“…before the surgical procedure. Orthotopic corneal transplantations were performed with wild-type (WT) or Rag 2/2 BALB/c mice as the recipient, using C57BL/6 mice as donors for allografts and BALB/c mice as donors for syngeneic grafts, as previously described (18,31). Initially, a central 2-mm full-thickness trephination of the recipient cornea was performed, followed by excision with corneal scissors.…”

Section: Orthotopic Corneal Transplantation and Graft Survival Evaluamentioning

confidence: 99%

“…Additionally, the relationship between corneal neovascularization and the previously mentioned immunological mechanisms remains poorly understood. Our laboratory demonstrated that the early recruited allospecific T cells play a critical role in the immunological rejection of high-risk vascularized corneal allografts (18). We hypothesize that the increased tempo and magnitude of T cell recruitment to the site of transplantation are essential for this process and that the presence of blood vessels in the cornea alters the immune response.…”

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confidence: 99%

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Immunological Disruption of Antiangiogenic Signals by Recruited Allospecific T Cells Leads to Corneal Allograft Rejection

Tan

Cruz-Guilloty

Medina-Mendez

et al. 2012

The Journal of Immunology

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Corneal transplantation is the most common solid organ transplantation. The immunologically privileged nature of the cornea results in high success rates. However, T cell-mediated rejection is the most common cause of corneal graft failure. Using antiangiogenesis treatment to prevent corneal neovascularization, which revokes immune privilege, prevents corneal allograft rejection. Endostatin is an antiangiogenic factor that maintains corneal avascularity. In this study, we directly test the role of antiangiogenic and immunological signals in corneal allograft survival, specifically the potential correlation of endostatin production and T cell recruitment. We report that 75% of the corneal allografts of BALB/c mice rejected after postoperative day (POD) 20, whereas all syngeneic grafts survived through POD60. This correlates with endogenous endostatin, which increased and remained high in syngeneic grafts but decreased after POD10 in allografts. Immunostaining demonstrated that early recruitment of allospecific T cells into allografts around POD10 correlated with decreased endostatin production. In Rag−/− mice, both allogeneic and syngeneic corneal grafts survived; endostatin remained high throughout. However, after T cell transfer, the allografts eventually rejected, and endostatin decreased. Furthermore, exogenous endostatin treatment delayed allograft rejection and promoted survival secondary to angiogenesis inhibition. Our results suggest that endostatin plays an important role in corneal allograft survival by inhibiting neovascularization and that early recruitment of allospecific T cells into the grafts promotes destruction of endostatin-producing cells, resulting in corneal neovascularization, massive infiltration of effector T cells, and ultimately graft rejection. Therefore, combined antiangiogenesis and immune suppression will be more effective in maintaining corneal allograft survival.

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Pathophysiology of Corneal Graft Rejection

Pérez¹,

Foulsham

Peterson

et al. 2019

Foundations of Corneal Disease

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Effect of CXCL-1/KC Production in High Risk Vascularized Corneal Allografts on T Cell Recruitment and Graft Rejection

Cited by 34 publications

References 41 publications

Chemokine and chemokine receptor expression analysis in target organs of acute graft-versus-host disease

Chemokine and chemokine receptor expression analysis in target organs of acute graft-versus-host disease

Immunological Disruption of Antiangiogenic Signals by Recruited Allospecific T Cells Leads to Corneal Allograft Rejection

Pathophysiology of Corneal Graft Rejection

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