Enrichment of CD8+ CD28- cytotoxic T cells in circulating lymphocytes of patients with ankylosing spondylitis

Introduction

In patients with ankylosing spondylitis (AS), HLA-B27 restricted cytotoxic T lymphocytes (CTLs) exist with specificity for arthritogenic bacteria, viral peptides or autoantigens. These MHC-class I restricted CTLs could maintain the inflammatory process even after the bacterial pathogen itself had been eradicated by antibacterial immune responses and thus be directly involved in the pathogenesis of spondylarthropathies. Phenotypically they are characterized by CD28-negativity and CD57/CD11a high-positivity. This study was performed to directly compare the relative number of CD8+ CTLs from AS patients with age-matched healthy controls. Until now only few data are available for the incidence of CD8+CD28- T cells in autoimmune diseases.

Methods

AS patients were recruited and examined at the Gasteiner Heilstollen Hospital. Controls were preselected by evaluating the proband's history and physical examination excluding an inflammatory or autoimmune diseases. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation, triple-stained for CD3, CD4, and CD28-antigens and analyzed on a FACScan flow cytometer.

Results

Peripheral blood was analyzed from 95 AS patients and 53 age -matched healthy controls (49,1 +/- 11,4 and 48.0 +/- 14.0 years old, respectively). In AS patients CD8+CD28- T cells are expanded more than in the age-matched population (41,2 +/- 17,7% and 18,6 +/- 7,6% (P < 0,0001), with regression lines y = 0,23x + 29,85 (R2 = 0,02) and y = 0,03x + 17,03 (R2 = 0,004), respectively). The percentage of CD8+CD28- T cells does not increase over the decades in healthy controls. Trends are described for increased percentages of CD8+CD28- T cells in patients with severe disease.

Conclusions

These data suggest that the fraction of CD8+CD28-T cells is not only increased in certain infectious diseases but also in patients diagnosed with AS. Increased percentages of CD8+CD28- T cells during ageing might be an artificial effect of undiagnosed infectious or autoimmune diseases. This finding further supports the hypothesis that increased levels of CD8+CD28- T cells can be considered pathogenic, comparable to benign monoclonal gammopathy.