The cornea is an immune privileged site and as such corneal transplants are very successful. However, in situations where this privilege is lost the failure rises substantially. To combat rejection inhibition of the immune responses depends on steroids and other immunosuppressive drugs, which are not always successful and sometimes have severe side-effects. In this paper the T cell receptor immunoglobulin and mucin domain (Tim) family member Tim1 was investigated. Tim1 is not expressed in naive CD4+ but is upregulated on the cell surface when activated, particularly on Th2 cells that are normally involved in allergic responses. To induce a high-risk transplant Balb/c mice were transplanted with corneas from C57BL/6 mice, which have different transplantation antigens and so will be recognised as foreign. Transplanted mice were either treated with RMT1-10, an anti-Tim1 monoclonal antibody or an isotype control. In RMT1-10 treated mice the numbers of effector immune cells were significantly decreased while T regulatory cells were significantly increased in the spleen, and allograft survival and corneal opacity were significantly increased. In vitro studies showed reduced expression of both IFN-Y and IL-4 in splenic CD4+ T cells from RMT1-10 treated animals. By comparison, expression of TGF-ß1, an anti-inflammatory cytokine was increased. Finally, RMT1-10 treated cells inhibited the delayed-type hypersensitivity in recipient mice, a model which supports a regulatory effect. The results suggest that inhibition of Tim1 can increase the regulatory arm of the immune response and decrease the inflammatory response, leading to increased allograft survival. The potential for such treatment in humans is of interest as unlike many diseases the timing of graft delivery and rejection is known and therefore delivery of inhibitory molecules easily determined.

Tim-1 blockade with RMT1-10 increases T regulatory cells and prolongs the survival of high-risk corneal allografts in mice.
Tan X, Jie Y, Zhang Y, et al.
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Graham Wallace

Birmingham and Midland Eye Centre, Birmingham, UK.

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