Depletion of regulatory T cells in a hapten‐induced inflammation model results in prolonged and increased inflammation driven by T cells. (March 2015)

• Record Type: Journal Article
• Authors: Christensen, A. D.; Skov, S.; Kvist, P. H.; Haase, C.
• Is Part Of: Clinical and experimental immunology. Volume 179:Number 3(2015:Mar.)
• Page Start: 485
• Page End: 499
• Publication Date: 2015-03
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12466
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Regulatory T cells (T<sub>regs</sub>) are known to play an immunosuppressive role in the response of contact hypersensitivity (CHS), but neither the dynamics of T<sub>regs</sub> during the CHS response nor the exaggerated inflammatory response after depletion of T<sub>regs</sub> has been characterized in detail. In this study we show that the number of T<sub>regs</sub> 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<sub>regs</sub> in the draining lymph nodes peaks at day 2. As expected, depletion of T<sub>regs</sub> 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‐10R) did not further increase the exaggerated inflammatory response in the T<sub>reg</sub>‐depleted mice. In the absence of T<sub>regs</sub>, 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<sub>regs</sub> 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.</p> </abstract>