CD27⁺ memory and CD27^- effector CD8⁺ T cells are responsible for a decreased production of proinflammatory cytokines in HLA B27-positive subjects

CER2682
2005 Vol.23, N°6
PI 0840, PF 0846
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PMID: 16396702 [PubMed]

Abstract

BACKGROUND AND OBJECTIVES:
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 TNFα, IFN&ggr;, IL-4 and IL-10.
RESULTS:
CD27⁺ CD45RA^- memory CD8⁺ T cells of HLA B27-positive subjects showed a significantly lower percentage of TNFα (median 71.4%) and IFN&ggr; production (median 69.7%) than HLA B27-negative controls (TNFα 85.1%; p ≤ 0.027; IFN&ggr; 82.7%, p ≤ 0.026). A similar result was also detected in CD27^- CD45RA⁺ effector CD8⁺ T cells of which 43.2% produced TNFα and 66.3% IFN&ggr;in HLA B27-positive subjects, respectively, compared to 75.6% TNFα and 84.4% IFN&ggr;producing T cells in HLA B27-negatives (p ≤ 0.045 and p ≤ 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 IFN&ggr;, TNFα, IL-4 or IL-10 producers nor the coexpression of IFN&ggr; 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.