We showed thatArthritis is a frequent and major complication of natural and experimental infection with Borrelia burgdorferi (1,5,30,34). Moreover, arthritis is induced following vaccination, with (14, 25) or without (28) challenge with B. burgdorferi. The immunologic events responsible for these B. burgdorferi-associated arthritides are poorly understood. We demonstrated that induction of chronic severe destructive arthritis following vaccination and challenge was dependent on B. burgdorferi-specific T lymphocytes (23). Treatment of vaccinated animals with anti-CD4 antibody prevented the development of severe destructive arthritis when the animals were challenged with the Lyme spirochete (24). Activated or primed CD4 ϩ T cells participated in the development of arthritis that included cartilage and bone erosion (24).Recently, we also showed that B. burgdorferi-vaccinated interferon gamma-deficient (IFN-␥ 0 ) mice challenged with B. burgdorferi developed a prominent chronic severe destructive osteoarthropathy (12). These results along with those of Brown and Reiner (6) present compelling evidence that interferon gamma (IFN-␥) does not play a major role in the induction or propagation of arthritis in the infection (6) or vaccinationchallenge (12) model of B. burgdorferi-associated arthritis. This suggests that other cytokines, chemokines, or other immune regulators are responsible for the induction of arthritis.

CD4؉ CD25 Our investigators showed previously that Borrelia burgdorferi-vaccinated gamma interferon-deficient (IFN-␥°) mice challenged with B. burgdorferi developed a prominent chronic destructive osteoarthropathy (13). The tibiotarsal joint of vaccinated and challenged mice displayed chronic hypertrophy and hyperplasia characterized by erosion of articular cartilage and focal destruction of bone. Treatment of vaccinated IFN-␥°m ice with anti-interleukin-17 (IL-17) antibody followed by challenge with B.

CD4؉ CD25 ؉ T cells are a population of regulatory T cells associated with control of arthritis in antiinterleukin-17 antibody-treated Borrelia-vaccinated and challenged gamma interferon-deficient mice. Here, we present direct evidence that adoptive transfer of enriched CD4 ؉ CD25 ؉ T cells from these mice can prevent the development of arthritis in Borrelia-vaccinated and challenged mice. These findings establish a major role for CD4؉ CD25 ؉ T cells in the prevention of arthritis in Borrelia-vaccinated and challenged animals.