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 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.
Barber
Linda D
LD
The Anthony Nolan Research Institute, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, United Kingdom. l.barber@rfc.ucl.ac.uk
Whitelegg
Alison
A
Madrigal
J Alejandro
JA
Banner
Nicholas R
NR
Rose
Marlene L
ML
D000328:Adult; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D015234:HLA-A Antigens / Q000032:analysis / Q000737:chemistry / Q000276:immunology; D015789:HLA-A2 Antigen; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D014746:Vimentin / Q000276:immunology*
D001323:Autoantibodies; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D014746:Vimentin; D007371:Interferon-gamma