Treg cell numbers and function in patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis.
OBJECTIVE
In a murine model of antibiotic-refractory Lyme arthritis, the numbers of Treg cells are dramatically reduced. The aim of this study was to examine Treg cell numbers and function in patients with antibiotic-refractory Lyme arthritis.


METHODS
CD4+ T cell subsets were enumerated in the peripheral blood (PB) and synovial fluid (SF) of 12 patients with antibiotic-refractory arthritis and 6 patients with antibiotic-responsive arthritis. Treg cell function was examined using Borrelia-specific and nonspecific Treg cell proliferation assays.


RESULTS
In both patient groups, interferon-gamma-positive Th1 cells in SF were abundant and enriched (approximately 50% of CD4+ T cells). In patients with antibiotic-refractory arthritis, the median percentages of FoxP3-positive Treg cells were significantly higher in SF than in PB (12% versus 6%; P = 0.03) or in SF from patients with antibiotic-responsive arthritis (12% versus 5%; P = 0.04). Moreover, in the antibiotic-refractory group, a higher percentage of Treg cells in SF correlated with a shorter duration until resolution of arthritis (r = -0.74, P = 0.006). In contrast, patients with fewer Treg cells had suboptimal responses to disease-modifying antirheumatic drugs and a longer duration of arthritis after antibiotic treatment, and they often required synovectomies for arthritis resolution. In each group, Treg cells in SF dampened Borrelia burgdorferi-specific proliferative responses, and in 2 patients with antibiotic-refractory arthritis, Treg cells were functional in nonspecific suppression assays.


CONCLUSIONS
Treg cells were functional in patients with antibiotic-refractory arthritis, and in some patients, higher numbers of these cells in SF appeared to participate in arthritis resolution. However, as in the murine model, patients with antibiotic-refractory arthritis and lower numbers of Treg cells seemed unable to achieve resolution of synovial inflammation.
Shen
Shiqian
S
Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Shin
Junghee J
JJ
Strle
Klemen
K
McHugh
Gail
G
Li
Xin
X
Glickstein
Lisa J
LJ
Drouin
Elise E
EE
Steere
Allen C
AC
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001170:Arthritis, Infectious / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D025065:Borrelia burgdorferi / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D049109:Cell Proliferation; D002648:Child; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005260:Female; D006801:Humans; D008193:Lyme Disease / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*; D055815:Young Adult
D000900:Anti-Bacterial Agents