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Reduced surface expression of transforming growth factor beta receptor type II in mitogen-activated T cells from

R J Capocasale1, R J Lamb, E C Vonderheid

  • 1Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 6, 1995
PubMed

Insights

Sézary syndrome (SzS) T cells show reduced surface TGF-beta receptor II (TGF beta RII) expression. This defect in receptor transport, not production, may drive SzS development.

Area of Science:

  • Immunology
  • Dermatology
  • Oncology

Background:

  • Sézary syndrome (SzS) is a leukemic form of cutaneous T-cell lymphoma.
  • SzS involves abnormal CD4+ T-cell proliferation and immune dysfunction.
  • Previous studies indicated a reduced response to TGF-beta in SzS T cells.

Purpose of the Study:

  • To investigate defects in transforming growth factor type beta receptor II (TGF beta RII) expression and transport in SzS.
  • To quantify surface and intracellular TGF beta RII levels in SzS CD4+ T cells.

Main Methods:

  • Developed a sensitive flow cytometry method.
  • Detected TGF beta RII on the surface and intracellularly in CD4+ T cells.
  • Compared SzS patient samples with normal CD4+ T cells.

Main Results:

  • CD4+ T cells from 9 out of 12 SzS patients showed significantly reduced surface TGF beta RII expression after mitogen stimulation.
  • Intracellular TGF beta RII levels were comparable between SzS patients and healthy controls.
  • A defect in TGF beta RII trafficking was observed in SzS T cells.

Conclusions:

  • Defective trafficking of TGF beta RII contributes to Sézary syndrome.
  • Reduced surface expression of this inhibitory receptor may impair T-cell regulation in SzS.
  • Targeting TGF beta RII transport could be a therapeutic strategy for SzS.

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