CD27+ memory and CD27- effector CD8+ T cells are responsible for a decreased production of proinflammatory cytokines in HLA B27-positive subjects.
OBJECTIVE
AS and other spondyloarthritides (SpA) are mostly chronic inflammatory rheumatic diseases characterised by a strong association with HLA B27. Recent data from our group have suggested that AS patients have a diminished secretion capacity of inflammatory cytokines, possibly associated with HLA B27. The aim of this study was to identify CD4+ and CD8+ T cell subsets responsible for the observed lower cytokine secretion capacity in HLA B27-positives.


METHODS
Highly purified (> 98%) CD4+ and CD8+ T cells of HLA B27-positive AS patients (n = 13), healthy HLA B27-positive (n = 7) and -negative controls (n = 9) were stimulated for 6h with PMA/ Ionomycin and, after fixation, stained for surface markers CD45RA and CD27 and cytokines TNFalpha, IFNgamma, IL-4 and IL-10.


RESULTS
CD27+ CD45RA- memory CD8+ T cells of HLA B27-positive subjects showed a significantly lower percentage of TNFalpha (median 71.4%) and IFNgamma production (median 69.7%) than HLA B27-negative controls (TNFalpha 85.1%; p < or = 0.027; IFNgamma 82.7%, p < or = 0.026). A similar result was also detected in CD27- CD45RA+ effector CD8+ T cells of which 43.2% produced TNFalpha and 66.3% IFNgamma in HLA B27-positive subjects, respectively, compared to 75.6% TNFalpha and 84.4% IFNgamma producing T cells in HLA B27-negatives (p < or = 0.045 and p < or = 0.062, respectively). For all CD4+ T cell subsets no significant differences between HLA B27-positive and HLA B27-negative donors were observed, regarding neither the frequency of IFNgamma, TNFalpha, IL-4 or IL-10 producers nor the coexpression of IFNgamma and IL-4 in memory subsets.


CONCLUSIONS
HLA B27-positive subjects are characterized by a low proinflammatory cytokine production in CD8+ effector and memory T cell subsets. This suggests an influence of HLA B27 on cytokine production in antigen-experienced CD8+ T cells.
Kohler
S
S
Campus Benjamin Franklin, Charité Berlin, Germany. ccsigi@drfz.de
Thiel
A
A
Rudwaleit
M
M
Sieper
J
J
Braun
J
J
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015796:HLA-B27 Antigen / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015415:Biomarkers; D015796:HLA-B27 Antigen; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha