HLA-B27-restricted antigen presentation by human chondrocytes to CD8+ T cells: potential contribution to local immunopathologic processes in ankylosing spondylitis.
OBJECTIVE
Analysis of the histopathologic features of hip arthritis in patients with ankylosing spondylitis (AS) has revealed accumulation of infiltrating mononuclear cells in the bone end plate and presence of hyaline articular cartilage that is not found in areas of total cartilage destruction. This study was undertaken to assess whether chondrocytes attract lymphocytes and whether cartilage chondrocytes from patients with AS have the potential to directly stimulate T cells in an HLA-restricted manner.


METHODS
Human HLA-B27+ T cell lines, specific for the Epstein-Barr virus-derived peptide EBNA258-266, and autologous chondrocytes, serving as nonprofessional antigen-presenting cells (APCs), were available for use in a model system to study chondrocyte functions in femoral head joint cartilage of patients with AS. Peptide functionality of cytotoxic T cells was assessed by flow cytometry, and cellular interactions were detected by fluorescence confocal microscopy.


RESULTS
When maintained in an alginate matrix, chondrocytes isolated from the femoral heads of patients with AS constitutively expressed type II collagen and CD80. When pulsed with the EBNA258-266 peptide, autologous chondrocytes functioned as APCs and, specifically, induced interferon-gamma production in CD8+ T cells. In mixed chondrocyte-T cell cultures, cell-cell contacts were dependent on the presence of the EBNA258-266 peptide. T cells adjacent to chondrocytes produced perforin and granzyme B; both molecules were found in focal aggregates, a prerequisite for antigen-specific lysis of target cells.


CONCLUSIONS
Antigen presentation through human chondrocytes allows the stimulation of peptide-specific CD8+ T cells. These results indicate that human chondrocytes can act as nonprofessional APCs, and suggest that there is an interferon-gamma-triggered autocrine loop of immune cell-mediated chondrocyte activation in the already inflamed environment. Thus, local HLA-dependent activation of peptide-specific cytotoxic CD8+ T cells by chondrocytes might contribute to inflammatory processes in the spondylarthritides.
Kuhne
Maren
M
Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Department of Gastroenterology, Infectiology and Rheumatology, Berlin, Germany.
Erben
Ulrike
U
Schulze-Tanzil
Gundula
G
Köhler
Dorothee
D
Wu
Peihua
P
Richter
F Jan
FJ
John
Thilo
T
Radbruch
Andreas
A
Sieper
Joachim
J
Appel
Heiner
H
D018122:B7-1 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D024043:Collagen Type II / Q000378:metabolism; D005260:Female; D053804:Granzymes / Q000378:metabolism; D015796:HLA-B27 Antigen / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008875:Middle Aged; D054353:Perforin / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology
D018122:B7-1 Antigen; D024043:Collagen Type II; D015796:HLA-B27 Antigen; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes