title: Dysregulation of CD4+CD25(high) T cells in the synovial fluid of patients with antibiotic-refractory Lyme arthritis.
abstract: 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 antibody-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.
  
  
  CONCLUSIONS
  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.
authors: Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors: Nalini K
authors: NK
authors: Vudattu
authors: Klemen
authors: K
authors: Strle
authors: Allen C
authors: AC
authors: Steere
authors: Elise E
authors: EE
authors: Drouin
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D016207:Cytokines / Q000032:analysis*; D004352:Drug Resistance, Microbial; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit; D008193:Lyme Disease / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013582:Synovial Fluid / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit