T-cells from advanced atherosclerotic lesions recognize hHSP60 and have a restricted T-cell receptor repertoire.
Atherosclerosis is a multifactorial, chronic-inflammatory disease for which the underlying cause remains unknown. It is also well documented that T-cells are among the first cells to migrate into the arterial intimal vessel layer, but their function there is still unexplained. Clinical and experimental data have provided evidence that atherosclerosis starts as an autoimmune reaction based on humoral and cellular immunity against a phylogenetically highly conserved stress protein, heat shock protein 60 (HSP60). In the present study, we phenotypically characterized T-cells from endarterectomized specimens of the carotid artery, and tested their reactivity to human HSP60. In addition, the T-cell receptor repertoire of the T-cell lines was defined by immunoscope analysis. We found a mixed population of CD4(+) and CD8(+) intralesional T-cells, with a slight predominance of CD8(+) cells. IFN-gamma production prevailed over IL-4 production. The T-cell reaction against human HSP60 was significantly increased in intralesional cells compared to peripheral T-cells. The lesion-derived T-cells showed an oligoclonally-restricted repertoire, in contrast to the polyclonal pattern of PBMC. These results clearly show that HSP60 is a major antigenic candidate, and that an oligoclonal T-cell expansion takes place in advanced human atherosclerotic lesions.
Rossmann
Andrea
A
Division of Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, Fritz-Pregl-Strasse 3/4, Innsbruck, Austria.
Henderson
Blair
B
Heidecker
Bettina
B
Seiler
Ruediger
R
Fraedrich
Gustav
G
Singh
Mahavir
M
Parson
Walther
W
Keller
Michael
M
Grubeck-Loebenstein
Beatrix
B
Wick
Georg
G
D000368:Aged; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002340:Carotid Artery Diseases / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018834:Chaperonin 60; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma