Functional characterization of Foxp3-specific spontaneous immune responses

Susanne Købke Larsen, S Munir, Anders Woetmann Andersen, Thomas Mørch Frøsig, Niels Ødum, I M Svane, J C Becker, Mads Hald Andersen

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Tumor-infiltrating CD4+CD25+ regulatory T cells (Tregs) are associated with an impaired prognosis in several cancers. The transcription factor forkhead box P3 (Foxp3) is generally expressed in Tregs. Here, we identify and characterize spontaneous cytotoxic immune responses to Foxp3-expressing cells in peripheral blood of healthy volunteers and cancer patients. These immune responses were directed against a HLA-A2-restricted peptide epitope derived from Foxp3. Foxp3-reactive T cells were characterized as cytotoxic CD8+ T cells. These cells recognized dendritic cells incubated with recombinant Foxp3 protein indicating that this protein was indeed internalized, processed and cross-presented in the context of HLA-A2. More importantly, however, Foxp3-specific T cells were able to specifically recognize Tregs. Similarly, Foxp3+ malignant T cells established from a Cutaneous T-cell lymphomas (CTCL) patient were readily killed by the Foxp3-specific cytotoxic T lymphocytes. The spontaneous presence of Foxp3-specific cytotoxic T-cell responses suggest a general role of such T cells in the complex network of immune regulation as such responses may eliminate Tregs, that is, suppression of the suppressors. Consequently, induction of Foxp3-specific cytotoxic T-cell responses appears as an attractive tool to boost spontaneous or therapeutically provoked immune responses, for example, for the therapy of cancer.
    Original languageEnglish
    JournalLeukemia
    Volume27
    Issue number12
    Pages (from-to)2332-2340
    Number of pages9
    ISSN0887-6924
    DOIs
    Publication statusPublished - 2013

    Keywords

    • Case-Control Studies
    • Cross Reactions
    • Enzyme-Linked Immunosorbent Assay
    • Flow Cytometry
    • Forkhead Transcription Factors
    • HLA-A2 Antigen
    • Humans
    • Lymphoma, T-Cell, Cutaneous
    • T-Lymphocytes, Cytotoxic
    • T-Lymphocytes, Regulatory

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