Potential Role of a Mismatched HLA-Specific CTL Clone Developed Pre-Transplant in Graft Rejection following Cord Blood Transplantation

Abstract 

Graft rejection is a serious complication in cord blood transplantation (CBT), but little is known about the mechanism of rejection. To investigate the potential role of T lymphocytes in graft rejection, we isolated a CD8⁺ cytotoxic T lymphocyte (CTL) clone of recipient origin from blood obtained from a patient with graft rejection after CBT from an HLA-mismatched unrelated donor. The isolated CTL clone specifically recognized an HLA-B^∗1501 molecule as an alloantigen, which was expressed in donor cells but not in recipient cells. The results of a microchimerism analysis specific for HLA-B^∗1501 and a polymerase chain reaction assay specific for the T cell receptor on DNA from pretransplant peripheral blood mononuclear cells revealed that the patient was exposed to HLA-B^∗1501 prior to CBT, and that the CTL clone was in the patient's blood prior to transplantation. The present study demonstrates a potential role for pretransplant CTL in graft rejection following CBT.

Key Words: Graft failure, HLA class I antigen, T lymphocyte, Microchimerism, Reduced-intensity stem cell transplantation