Open AccessDysregulation of CD4+CD25 high T Cells in the Synovial Fluid of Patients With Antibiotic‐Refractory Lyme Arthritis
Author(s) -
Vudattu Nalini K.,
Strle Klemen,
Steere Allen C.,
Drouin Elise E.
Publication year - 2013
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.37910
Subject(s) - il 2 receptor , medicine , arthritis , synovial fluid , immunology , foxp3 , population , tumor necrosis factor alpha , immune system , t cell , pathology , alternative medicine , environmental health , osteoarthritis
Objective To examine the role of immune dysregulation in antibiotic‐refractory Lyme arthritis by comparing the phenotype, frequency, and function of CD4+ Teff cells and Treg cells in patients with antibiotic‐ responsive arthritis and patients with antibiotic‐refractory arthritis. Methods Matched peripheral blood and synovial fluid samples from 15 patients with antibiotic‐responsive arthritis were compared with those from 16 patients with antibiotic‐refractory arthritis, using flow cytometry, suppression assays, and cytokine assays. Results Critical differences between the 2 patient groups were observed in the synovial fluid CD4+CD25 high population, a cell subset usually composed of FoxP3‐positive Treg cells. In patients with antibiotic‐refractory arthritis, this cell population often had fewer FoxP3‐positive cells and a greater frequency of FoxP3‐negative (Teff) cells compared with patients with antibiotic‐responsive arthritis. Moreover, the expression of glucocorticoid‐induced tumor necrosis factor receptor and OX40 on CD4+CD25 high cells was significantly higher in the antibiotic‐refractory group. Suppression assays showed that CD4+CD25 high cells in patients with antibiotic‐refractory arthritis did not effectively suppress proliferation of CD4+CD25− cells or secretion of interferon‐γ and tumor necrosis factor α, whereas those cells in patients with antibiotic‐responsive arthritis did suppress proliferation of CD4+CD25− cells and secretion of interferon‐γ and tumor necrosis factor α. Finally, in the antibiotic‐refractory group, higher ratios of CD25 high FoxP3‐negative cells to CD25 high FoxP3‐positive cells correlated directly with a longer duration of arthritis after antibiotic treatment. Conclusion Patients with antibiotic‐refractory Lyme arthritis often have lower frequencies of Treg cells, higher expression of activation coreceptors, and less effective inhibition of proinflammatory cytokines. This suggests that immune responses in these patients are excessively amplified, leading to immune dysregulation and antibiotic‐refractory arthritis.