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

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 CD25 prior to sensitization led to a prolonged and sustained inflammatory response which was dependent upon CD8 T cells, and co-stimulatory blockade with cytotoxic T lymphocyte antigen-4-immunoglobulin ( CTLA-4- Ig) 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. [ABSTRACT FROM AUTHOR]