Significant frequencies of T cells with indirect anti-donor specificity inheart graft recipients with chronic rejection

Background-The purpose of this study was to determine whether T cells with indirect allospecificity could be detected in heart transplant recipients w ith chronic rejection. Methods and Results-Human T-cell clones were used to determine the most eff ective way to deliver major histocompatibility complex alloantigens for ind irect presentation. Seven allograft recipients with evidence of progressive , chronic rejection were selected. Four heart graft recipients with no evid ence of chronic rejection were used as controls. Peripheral blood T cells a nd antigen-presenting cells from the recipients were cultured with frozen/t hawed stored donor cells or major histocompatibility complex class I-derive d synthetic peptides in limiting dilution cultures and then compared with c ontrols using tetanus toroid and frozen/thawed third-party cells with no hu man leukocyte antigens in common with the donor. In 5 of 7 patients analyze d who had chronic rejection, elevated frequencies of T cells with indirect, anti-donor specificity (iHTLf) were detected. No such elevated iHTLf were detected in recipients without chronic rejection. Discussion-iHTLf can be obtained from human transplant recipients, which su pports the contention that the indirect pathway is involved in chronic tran splant rejection.