The role of co-stimulation in corneal allograft rejection

Erwin Schrödinger Fellowship J 1909 The role of co-stimulation in corneal allgograft rejection Navid ARDJOMAND 06.03.2000 Immunological graft rejection is the most common reason for korneal transplant failure. T cells and antigen presenting cells are known to play a key role in corneal graft rejection. Blockade of the CD28-B7 pathway has been shown to prolong skin and cardiac allograft survival in a mouse model. Gebhardt et al. demonstrated recently (Cornea 1999;18:314) that incubation of corneal grafts in storage medium containing CTLA-4 Ig prior to transplantation prolong corneal allograft survival. This study should investigate the hypothesis that lymphoclyte co- stimulation via (i) CD28 and (ii) CD40 is essential for corneal allograft rejection, using a mouse model. At first the importance of the CD 28-B7 pathway is going to be studied. We examine corneal graft survival in CD28 knock-out mice compared to wild-type control mice with functioning CD28 molecules. The second part of the project deals with the importance of the CD40-CD154 pathway. In this case M158 (monoclonal rat IgG antibody against mouse CD154 antigen) is used by i.p. application to block the CD40-CD154 pathway. The above described control group is going to be comared with M158 treated mice. In case of a positive influence of the CD154 blockade on corneal graft survival, we will additionally investigate corneal graft survival in mice with CD28 knock-out in combination with M158 treatment. The 3rd part of the experiment should evaluate the combined blockade of the CD28-B7 and CD40-CD154 pathways of the immune system.