T helper 1 response is dominant and localized to the synovial fluid in patients with Lyme arthritis

Cytokines produced by subsets of CD4+ T helper cells responding to an infection influences the efficiency with which the host is able to mount a protective immune response. In an attempt to elucidate the population of active cells involved in the propagation of Lyme arthritis we have utilized intracellular cytokine staining to analyze the polyclonal immune response at the single cell level. We have determined the Th phenotype in the synovial fluid of patients with a variety of chronic inflammatory arthritides, including patients representative of the spectrum of Lyme arthritis. Th1 cells dominate the immune response in the synovial fluid of patients with Lyme as well as those with rheumatoid or other types of chronic inflammatory arthritis. In addition, the severity of Lyme arthritis directly correlates with the ratio of Th1 to Th2 cells in the synovial fluid, such that the larger the effusion, the higher the ratio (r = 0.67, p < 0.05). These results suggest that Th1 cells play a direct role in the pathogenesis of the inflammatory process seen in Lyme arthritis, and that Th2 cells modulate the pro-inflammatory response generated by Th1 cells in the joint. Finally, we identify Th1 cells specific for outer surface protein A of Borrelia burgdorferi, the agent of Lyme disease. These cells are restricted to patients with Lyme arthritis and are localized to the joint. Furthermore, they persist in patients with prolonged antibiotic treatment-resistant Lyme arthritis, suggesting the possibility of an autoimmune process.