Lyme Arthritis Synovial γδ T Cells Respond to <i>Borrelia burgdorferi</i> Lipoproteins and Lipidated Hexapeptides

Abstract

Abstract Lyme arthritis synovial fluid contains a large proportion of γδ T cells that proliferates upon stimulation with the causative spirochete, Borrelia burgdorferi. A panel of Borrelia-reactive γδ T cell clones was derived from synovial fluid of two patients with Lyme arthritis. Each of six γδ clones from one patient used the Vδ1 TCR segment but had otherwise unique CDR3 sequences and diverse Vγ segment usage. Stimulation of the Vδ1 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-γδ 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 Vδ1 T cells may mediate an innate immune response to common lipoprotein products of spirochetes.