Detection of vimentin-specific autoreactive CD8+ T cells in cardiac transplant patients

Background. Evidence is emerging that autoimmunity can play a role in allograft rejection. Reports have described the presence of autoantibodies in transplant patients and CD4(+) autoreactive T cells in rodent models of allograft rejection. The objective of this study was to seek evidence of CD8(+) T-cell-mediated autoimmunity in the transplant setting. The authors have previously observed autoimmunity to the non-polymorphic cytoskeletal protein vimentin in cardiac transplant patients. In this study, vimentin antibody-positive patients were screened for the presence of vimentin-specific self-major histocompatibility complex class I-restricted CD8(+) T cells. Methods. Two peptide sequences from vimentin that bound HIA-A*0201 were identified and fluorochromelabeled A*0201 tetramers with each peptide were constructed to screen for vimentin-specific T cells. Results. Tetramer-binding CD8(+) T cells were detected in peripheral blood lymphocytes from two of six patients after expansion by in vitro stimulation with peptide. Tetramer-binding T cells produced interferon-gamma in an antigen-specific fashion. No autoreactive T cells specific for vimentin were detected after peptide stimulation of T cells from eight healthy A*0201-positive volunteers. Conclusions. This finding is the first evidence of CD8(+) T-cell-mediated autoimmunity in human transplant patients.