IL-10 Deficiency Reveals a Role for TLR2-Dependent Bystander Activation of T Cells in Lyme Arthritis

Sarah K. WhitesideJeremy P. SnookYing MaF. Lynn SondereggerColleen FisherCharisse PetersenJames F. ZacharyJune L. RoundMatthew A. Williams and Janis J. Weis

T cells predominate the immune responses in the synovial fluid of patients with persistent Lyme arthritis; however, their role in Lyme disease remains poorly defined. Using a murine model of persistent Lyme arthritis, we observed that bystander activation of CD4+ and CD8+ T cells leads to arthritis-promoting IFN-γ, similar to the inflammatory environment seen in the synovial tissue of patients with posttreatment Lyme disease. TCR transgenic mice containing monoclonal specificity toward non–Borrelia epitopes confirmed that bystander T cell activation was responsible for disease development. The microbial pattern recognition receptor TLR2 was upregulated on T cells following infection, implicating it as marker of bystander T cell activation. In fact, T cell–intrinsic expression of TLR2 contributed to IFN-γ production and arthritis, providing a mechanism for microbial-induced bystander T cell activation during infection. The IL-10–deficient mouse reveals a novel TLR2-intrinsic role for T cells in Lyme arthritis, with potentially broad application to immune pathogenesis.


  • S.K.W. was supported by National Institutes of Allergy and Infectious Disease Research Training Grant T32 AI055434. J.P.S. was supported by the American Association of Immunologists Careers in Immunology Fellowship Program. J.L.R. was supported by the Edward Mallinckrodt Jr. Foundation, the Pew Charitable Trusts Scholars Program, National Science Foundation CAREER Award IOS-1253278, a David and Lucile Packard Foundation Fellowship in Science and Engineering, National Institute of Allergy and Infectious Diseases Grants K22 AI95375, AI107090, and AI109122, and by National Institutes of Health Directors Innovator Award DP2AT008746. J.J.W. and M.A.W. were supported by National Institutes of Health Grant R01 AI32223. J.J.W. was supported by National Institutes of Health Grants R01 AR43521 and R21AI114462. Flow cytometry cell sorting was supported by National Center for Research Resources/National Institutes of Health Grant 1S10RR026802-01.

  • The online version of this article contains supplemental material.