Borrelia burgdorferi-specific T lymphocytes induce severe destructive Lyme arthritis

Abstract

This is the first documentation that Borrelia burgdorferi-specific T lymphocytes are involved in the pathogenesis of Lyme arthritis. We present direct evidence that T lymphocytes obtained from inbred LSH hamsters vaccinated with a whole-cell preparation of Formalin-inactivated B. burgdorferi sensu stricto isolate C-1-11 in adjuvant conferred on naive recipient hamsters the ability to develop severe destructive arthritis when challenged with B. burgdorferi sensu stricto isolates C-1-11 and 297. By contrast, recipients infused with normal T lymphocytes and challenged with B. burgdorferi sensu stricto isolates C-1-11 and 297 failed to develop severe destructive arthritis. The T lymphocytes transferred were obtained from the lymph nodes of vaccinated and nonvaccinated hamsters by depleting B lymphocytes by using monoclonal antibody 14-4-4s (< 1% B lymphocytes by flow cytometric analysis). The enriched T lymphocytes showed enhanced proliferation to stimulation with concanavalin A and failed to respond to lipopolysaccharide. Moreover, only the enriched T lymphocytes from vaccinated hamsters proliferated on exposure to a whole-cell preparation of B. burgdorferi sensu stricto isolate C-1-11 in the presence of mitomycin-treated syngeneic antigen-presenting cells. These results demonstrate that B. burgdorferi-specific T lymphocytes primed by vaccination with a whole-cell preparation of inactivated B. burgdorferi sensu stricto isolate C-1-11 in adjuvant are involved in the development of severe destructive arthritis. Additional experiments are needed to define the precise mechanism(s) responsible for the development of Lyme arthritis.