Depletion of regulatory T cells in a hapten‐induced inflammation model results in prolonged and increased inflammation driven by T cells

Summary Regulatory T cells ( T regs ) are known to play an immunosuppressive role in the response of contact hypersensitivity ( CHS ), but neither the dynamics of T regs during the CHS response nor the exaggerated inflammatory response after depletion of T regs has been characterized in detail. In this study we show that the number of T regs in the challenged tissue peak at the same time as the ear‐swelling reaches its maximum on day 1 after challenge, whereas the number of T regs in the draining lymph nodes peaks at day 2. As expected, depletion of T regs by injection of a monoclonal antibody to CD 25 prior to sensitization led to a prolonged and sustained inflammatory response which was dependent upon CD 8 T cells, and co‐stimulatory blockade with cytotoxic T lymphocyte antigen‐4‐immunoglobulin ( CTLA‐ 4‐ I g) suppressed the exaggerated inflammation. In contrast, blockade of the interleukin ( IL) ‐10‐receptor ( IL ‐10 R ) did not further increase the exaggerated inflammatory response in the T reg ‐depleted mice. In the absence of T regs , the response changed from a mainly acute reaction with heavy infiltration of neutrophils to a sustained response with more chronic characteristics (fewer neutrophils and dominated by macrophages). Furthermore, depletion of T regs enhanced the release of cytokines and chemokines locally in the inflamed ear and augmented serum levels of the systemic inflammatory mediators serum amyloid ( SAP) and haptoglobin early in the response.