T-cell responses to versican in ankylosing spondylitis.
The objective of our study was to undertake a systematic analysis of the T-cell response to the proteoglycan versican G1-globular domain (VG1) in ankylosing spondylitis (AS) as immunity to VG1 in mice can induce a pathology closely resembling AS. Peripheral blood lymphocytes from 36 AS patients and 33 healthy controls were incubated with recombinant human VG1 in culture for 6 h. T-cell responses were assessed by FACS analyses using mAb against surface expression of the activation marker CD69 and against the intracellular cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha. T cells activated by exposure to versican were determined by assessing the percentage of CD4+ or CD8+ T cells that were CD69/cytokine double-positive cells as compared to isotype control staining. In the AS patients, exposure to VG1 resulted in increased expression by CD4+ T cells of IFN-gamma in 55.6% of patients and of TNF-alpha in 52.8% of patients. In the controls, only 36.4% of subjects demonstrated an IFN-gamma response and 36.4% demonstrated a TNF-alpha response (P value 0.148, 0.227, respectively). With respect to CD8+ T-cell responses, versican stimulation enhanced IFN-gamma expression in 44.4% of AS patients and 39.4% of controls, and enhanced TNF-alpha response in 50.0% of AS patients and 39.4% of controls (P value 0.620, 0.327, respectively). Although, there was no statistically significant difference in the magnitude of the IFN-γ or TNF secretion by CD4+ T cells and CD8+ T cells between AS and controls, our results demonstrate an enhanced T-cell response to VG1 in AS.
Kim
Tae-Jong
TJ
Department of Rheumatology, Research Institute of Medical Sciences, Chonnam National University Medical School and Hospital, Gwangju, South Korea.
Kim
Tae-Hwan
TH
Lee
Hyun-Joo
HJ
Lee
Bitnara
B
Robin Poole
A
A
Inman
Robert D
RD
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D013167:Spondylitis, Ankylosing / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D053675:Versicans / Q000276:immunology*; D055815:Young Adult; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007371:Interferon-gamma; D037181:Lectins, C-Type; D014409:Tumor Necrosis Factor-alpha; D053675:Versicans; D000099192:CD69 Antigens