C57BL/6 mice deficient in TLR2 develop more severe arthritis following infection with Borrelia burgdorferi than do wild-type C57BL/6 mice, and this increase is suppressed by the simultaneous presence of the scid mutation. This suggested a requirement for lymphocytes in the development of subacute Lyme arthritis in TLR2(-/-) mice, a feature not commonly associated with this arthritis. The increased pathology of B. burgdorferi-infected TLR2(-/-) mice was also accompanied by an increase in mononuclear cell infiltration. In this study, T cells were found to be responsible for the increase in mononuclear cells in infected TLR2(-/-) C3H mice. Accordingly, transcripts for the IFN-inducible T cell chemokines, CXCL9 and CXCL10, were greatly enhanced in joint tissue from TLR2(-/-) mice, as were transcripts for a prototypical IFN-inducible gene IFN-gamma-induced GTPase (igtp). Treatment of murine synovial cells with sonicated B. burgdorferi resulted in induction of transcripts for chemokines and other IFN-inducible genes, irrespective of the presence of TLR2. The presence of T lymphocytes greatly enhanced the transcriptional response of synovial cells. These results suggest that the increased inflammatory cell infiltration in TLR2(-/-) C3H mice is the result of localized overproduction of T cell attracting chemokines.