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October 29, 2004Blood

Cutaneous T-cell lymphoma: malignant proliferation of T-regulatory cells

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Authors

CBCarole L. BergerThe Wistar InstituteRTRobert E. TigelaarYale UniversityJCJustine V. CohenHarvard University

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Implication

In vitro study reveals dendritic cells induce a regulatory T-cell phenotype in cutaneous T-cell lymphoma, indicating a mechanism for tumor-driven immunosuppression.

Key Points

  • To determine whether dendritic cell presentation of apoptotic tumor antigens triggers T-cell receptor activation and drives cutaneous T-cell lymphoma cells to adopt an immunosuppressive regulatory phenotype.
  • Examined CD4+ cutaneous T-cell lymphoma (CTCL) cells in an in vitro model co-cultured with autologous immature dendritic cells loaded with apoptotic CTCL cells or normal CD4+ T cells.
  • Assessed T-cell receptor activation, calcium mobilization, and the expression of regulatory markers including CD25, CTLA-4, FoxP3, IL-10, and TGF-beta.
  • Evaluated the requirement of antigen presentation by applying blocking agents against dendritic cell major histocompatibility complex (MHC) class 2 expression and intracellular transport.
  • Dendritic cells loaded with apoptotic cells stimulated CTCL T-cell receptors, triggering calcium mobilization, membrane down-regulation of CD3/TCR, and up-regulation of CTLA-4.
  • Stimulated CTCL cells acquired a regulatory T-cell phenotype characterized by FoxP3 expression, secretion of IL-10 and TGF-beta, and suppression of antigen-driven IL-2 and IFN-gamma production in normal T cells.
  • Blocking dendritic cell MHC class 2 expression or transport effectively inhibited the phenotypic conversion of CTCL cells into regulatory T cells.

Cite This Study

Berger et al. (2004) studied this question.

synapsesocial.com/papers/6a715ece2163a0a01bc58435https://doi.org/10.1182/blood-2004-06-2181
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Also Consider

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