The potential of antibody‐based immunosuppressive agents for corneal transplantation

Thiel, Michael; Coster, Douglas J.; Williams, Keryn A.

doi:10.1046/j.0818-9641.2002.01145.x

Cited by 17 publications

(9 citation statements)

References 150 publications

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“…CD4 + T cells are important in controlling the different mechanisms involved in corneal graft rejection and are thus a target for evaluating therapeutic interventions designed to prevent corneal allograft rejection (29). In the present study, it was observed that treatment with anti-CD154 mAb significantly reduced the frequency of total CD4 + T cells that infiltrated the ipsilateral draining lymph nodes, spleens and corneal grafts.…”

Section: Discussionmentioning

confidence: 99%

CD154 blockade modulates the ratio of Treg to Th1 cells and prolongs the survival of allogeneic corneal grafts in mice

Tan

Zeng

Jin

et al. 2014

Experimental and Therapeutic Medicine

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Administration of anti-CD154 monoclonal antibody (mAb) may prolong the survival of an allograft; however, the associated therapeutic mechanisms remain poorly understood. This study aimed to evaluate the effects of anti-CD154 mAb on T-cell responses in a mouse model of corneal allograft transplantation. BALB/c mice were transplanted with corneal grafts from C57BL/6 mice and treated intraperitoneally with 250 μg anti-CD154 mAb or isotype IgG on days 0, 3 and 6 post surgery. The transparency of the corneal grafts was evaluated for potential rejection signs by slit-lamp biomicroscopy and histopathology. The percentages of CD4+ T, Tim-3+CD4+ T helper (Th) 1 and CD4+CD25+Foxp3+ regulatory T cells (Tregs) in the spleen, ipsilateral draining lymph nodes and corneal grafts, and the frequency of splenic IFN-γ+ and IL-10+ expression in CD4+ T cells were determined by flow cytometry. Moreover, the ratio of Tregs to Th1 cells was calculated and the suppressive activity of splenic Tregs was measured. Anti-CD154 neutralization significantly prolonged the survival of the corneal allograft (P=0.0012) and reduced the numbers of inflammatory infiltrates in the corneal graft. In the spleen and lymph nodes, anti-CD154 treatment reduced the frequency of CD4+ T cells, Tregs and particularly Th1 cells. In the corneal allografts, anti-CD154 treatment downregulated graft-infiltrated CD4+ T cells and Th1 cells, but increased graft-infiltrated Tregs. Furthermore, anti-CD154 treatment increased the frequency of splenic IL-10+CD4+ T cells and decreased the concentration of splenic IFN-γ+CD4+ T cells. As a result, the ratio of Tregs to Th1 cells in the anti-CD154-treated recipients increased. Anti-CD154 treatment did not enhance the suppressive activity of Tregs in the recipients. The results indicate that the therapeutic effects of anti-CD154 mAb on prolonging the survival of the corneal allograft may be associated with an increased ratio of Tregs to Th1 cells in mice.

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Section: Discussionmentioning

confidence: 99%

CD154 blockade modulates the ratio of Treg to Th1 cells and prolongs the survival of allogeneic corneal grafts in mice

Tan

Zeng

Jin

et al. 2014

Experimental and Therapeutic Medicine

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“…Monoclonal antibodies and other biologics are not used routinely in corneal transplantation, but may be useful for both prophylaxis and for rescue after graft rejection (reviewed in [99,84]). CAMPATH-1H, in particular, has been shown to be effective in rescuing corneal grafts undergoing acute rejection.…”

Section: Immunosuppression For Corneal Transplantationmentioning

confidence: 99%

The Immunobiology of Corneal Transplantation

Williams

Coster

2007

Transplantation

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Corneal allotransplantation is highly successful in the short term, but much less successful in the longer term. Many corneal grafts in recipients with corneal neovascularization or the sequelae of ocular inflammation undergo irreversible rejection, despite topical immunosuppression with glucocorticosteroids. Sensitization to cornea-derived alloantigen proceeds by both direct and indirect routes, but the anatomic location of sensitization remains unclear. Multiple and redundant mechanisms operate in the effector phase of corneal graft rejection, which is largely cell-mediated rather than antibody-mediated. Human leukocyte antigen matching may improve outcomes in high-risk patients but systemic immunosuppression is frequently ineffective and is seldom used.

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“…44 Monoclonal antibodies and other biologics are not used routinely in corneal transplantation, but may be useful for both prophylaxis and for rescue after graft rejection. 30,45 CAMPATH-1H, a monoclonal antibody that rapidly induces lymphopenia after IV infusion, has been shown to be effective in rescuing corneal grafts undergoing acute rejection. The toxicity profile of this drug, which is licensed for the treatment of leukemia, is such that it is not recommended in corneal transplantation.…”

Section: Novel Agentsmentioning

confidence: 99%