gms | German Medical Science

Introduction: The rat NKC mapping on chromosome 4 is encompassing several gene families and single copy genes coding for cell surface expressed proteins with a C-type lectin-like structure. The majority of these proteins function as receptors (e.g. on NK-cells) inducing either activating or inhibitory signals following engagement with their physiological ligands. As many NKC-genes are polymorphic, several NKC-haplotypes exist. LEW and LEW.TO-NKC are NKC-congenic rat strains sharing the same genetic background but carrying different NKC-haplotypes. Using these strains as allograft recipients and the MHC-disparate strain LEW.1U as donor we have analysed whether a difference in NKC-haplotype affects rejection in a MHC-mismatched setting of skin transplantation.

Materials and methods: Skin transplantations were performed without immunosuppression using 10 weeks old male rats. Elimination of the NK-cell population in vivo was achieved by a single intravenous injection of 500 µg of mAb HT30 raised against rat NKR-P1A and developed by our group.

Results: Solely NKC-disparate (LEW → LEW.TO-NKC; n=4) or genetically identical (LEW → LEW; n=3) skin grafts were not rejected. Interestingly, skin grafts exhibiting a combined MHC-/NKC-disparity (LEW.1U → LEW.TO-NKC; n=10) survived significantly longer (MST 14.2±1.93 d) than exclusively MHC-disparate skin grafts (LEW.1U → LEW; n=10; MST 10.7±1.49 d). Elimination of the recipients´ NK-cell population (n=5) before transplantation of MHC-/NKC-disparate skin grafts resulted in a reduction of the survival time to 9 days. By contrast, in LEW.TO-NKC control animals (n=2) treated with an irrelevant antibody of the same isotype MHC-/NKC-disparate grafts survived for 12.5 days.

Conclusion: Thus, an additional NKC-difference can lead to a prolongation of graft survival of MHC-disparate skin grafts. This beneficial effect of NKC-disparity can be abrogated by antibody-mediated depletion of recipient´s NK-cells. It is assumed that MHC-disparate antigen presenting cells emigrating from the graft are preferentially eliminated by recipient NK-cells already early after transplantation rendering the graft less immunogenic.