Lyme arthritis synovial gamma delta T cells respond to Borrelia burgdorferi lipoproteins and lipidated hexapeptides.
Lyme arthritis synovial fluid contains a large proportion of gamma delta T cells that proliferates upon stimulation with the causative spirochete, Borrelia burgdorferi. A panel of Borrelia-reactive gamma delta T cell clones was derived from synovial fluid of two patients with Lyme arthritis. Each of six gamma delta clones from one patient used the V delta 1 TCR segment but had otherwise unique CDR3 sequences and diverse V gamma segment usage. Stimulation of the V delta 1 clones was optimal in the presence of Borrelia, dendritic cells, and exogenous IL-2, which was reflected by proliferation, TCR down-modulation, as well as induction of CD25 and Fas ligand expression. Stimulation by B. burgdorferi-pulsed dendritic cells withstood chemical fixation and was not restricted to class I or class II MHC, CD1a, CD1b, or CD1c. In contrast, anti-gamma delta antibody potently inhibited proliferation. Extraction of B. burgdorferi lipoproteins with Triton X-114 enriched for the stimulatory component. This was confirmed using lipidated vs nonlipidated hexapeptides of Borrelia outer surface proteins. These observations suggest that synovial V delta 1 T cells may mediate an innate immune response to common lipoprotein products of spirochetes.
Vincent
M S
MS
Department of Medicine, University of Vermont College of Medicine, Burlington 05405-0068, USA.
Roessner
K
K
Sellati
T
T
Huston
C D
CD
Sigal
L H
LH
Behar
S M
SM
Radolf
J D
JD
Budd
R C
RC
D000293:Adolescent; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001426:Bacterial Proteins / Q000276:immunology; D001483:Base Sequence; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D002648:Child; D002999:Clone Cells / Q000276:immunology / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D005404:Fixatives; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008074:Lipoproteins / Q000276:immunology*; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013144:Spirochaetales / Q000276:immunology; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D005404:Fixatives; D007166:Immunosuppressive Agents; D008074:Lipoproteins; D009842:Oligopeptides; D016692:Receptors, Antigen, T-Cell, gamma-delta