Transplantation · 2004
Detection of vimentin-specific autoreactive CD8+ T cells in cardiac transplant patients.
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Barber Linda D, Whitelegg Alison, Madrigal J Alejandro, Banner Nicholas R, Rose Marlene L
Аннотация
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 author have previously observed autoimmunity to the non-polymorphic cytoskeletal protein vimentin in cardia 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 HLA-A*0201 were identified and fluorochrome-labeled 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.
METHODS: Two peptide sequences from vimentin that bound HLA-A*0201 were identified and fluorochrome-labeled 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.