Natural killer-cell activity after human renal transplantation in relation to killer immunoglobulin-like receptors and human leukocyte antigen mismatch.
BACKGROUND
Natural killer (NK) cells use killer immunoglobulin-like receptors (KIR) that bind to self-class I major histocompatibility complex (MHC) molecules to prevent killing of autologous cells. Mismatched allografts, which do not express recipient MHC class I molecules, can therefore be potential targets for NK-cell killing. In our living related-unrelated renal transplantation program, donor-recipient pairs vary in the amount of both HLA and KIR genes they share. This provides us with a unique opportunity to dissect the influence of KIR on NK-cell function after transplantation.


METHODS
Recipient NK cells were used in a cytotoxicity assay against donor peripheral blood mononuclear cells 2 days before, on the day of, and 3 days after transplantation. Results were correlated to HLA-KIR compatibility between donor and recipient.


RESULTS
NK killing, in a direct ex vivo setting, was demonstrated to be HLA mismatch dependent. Recipient NK antidonor cytotoxicity was unaltered despite having received 2 days' treatment with cyclosporine A before transplantation. However, cytotoxicity increased 3 days after transplantation in 71% of recipients. Recipients exhibiting increased NK cytotoxicity against their donors after transplantation were found to possess more activating KIR genes specific for donor class I MHC molecules than those in whom killing activity did not increase (P<0.04).


CONCLUSIONS
NK cells are activated after transplantation despite quadruple immunosuppression, suggesting that recipient NK-cell cytotoxicity against the donor may be a previously unrecognized area of the rejection process, especially in poorly matched donor-recipient pairs where the recipient may not express the correct repertoire of inhibitory receptors to prevent killing of donor cells.
Vampa
Maria Luisa
ML
Department of Nephrology and Transplantation, Guy's Hospital, London, United Kingdom.
Norman
Paul J
PJ
Burnapp
Lisa
L
Vaughan
Robert W
RW
Sacks
Steven H
SH
Wong
Wilson
W
D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D005260:Female; D006680:HLA Antigens / Q000032:analysis* / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D054340:Receptors, KIR; D013997:Time Factors; D014019:Tissue Donors
D006680:HLA Antigens; D007166:Immunosuppressive Agents; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D016572:Cyclosporine