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 a n infection influences the efficiency with which the host is able to m ount a protective immune response. In an attempt to elucidate the popu lation of active cells involved in the propagation of Lyme arthritis w e have utilized intracellular cytokine staining to analyze the polyclo nal immune response at the single cell level, We have determined the T h phenotype in the synovial fluid of patients with a variety of chroni c inflammatory arthritides, including patients representative of the s pectrum of Lyme arthritis. Th1 cells dominate the immune response in t he synovial fluid of patients with Lyme as well as those with rheumato id or other types of chronic inflammatory arthritis. In addition, the severity of Lyme arthritis directly correlates with the ratio of Th1 t o 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 p rocess seen in Lyme arthritis, and that Th2 cells modulate the pro-inf lammatory response generated by Th1 cells in the joint. Finally, we id entify Th1 cells specific for outer surface protein A of Borrelia burg dorferi, the agent of Lyme disease, These cells are restricted to pati ents 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.