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The Journal of Immunology, 1998, 161: 5762-5771.
Copyright © 1998 by The American Association of Immunologists

Lyme Arthritis Synovial {gamma}{delta} T Cells Respond to Borrelia burgdorferi Lipoproteins and Lipidated Hexapeptides1

Michael S. Vincent*, Karen Roessner*, Timothy Sellati{dagger}, Christopher D. Huston*, Leonard H. Sigal§, Samuel M. Behar, Justin D. Radolf{dagger},{ddagger} and Ralph C. Budd2,*

* Divisions of Immunobiology and Rheumatology, Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405; Departments of {dagger} Internal Medicine and {ddagger} Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75235; § Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903; and Lymphocyte Biology Section, Division of Rheumatology and Immunology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115

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.




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