Increased expression of CTLA-4 in malignant T-cells from patients with mycosis fungoides -- cutaneous T cell lymphoma

J Invest Dermatol. 2006 Jan;126(1):212-9. doi: 10.1038/sj.jid.5700029.

Abstract

Mycosis fungoides (MF) is a low-grade lymphoma of cluster of differentiation (CD)4+, CD45RO+, cutaneous leukocyte antigen (CLA)+ T cells that homes to the skin. To understand the functional abnormalities in this disease, we study the regulation of cytotoxic T-lymphocyte antigen (CTLA)-4 in peripheral blood mononuclear cells (PBMCs) from patients with MF. CTLA-4 is a costimulatory molecule for T cells that functions in immunoregulation. Unlike the expression of CD28, which is expressed constitutively on T cells, CTLA-4 expression is highly regulated. In the analysis of PBMCs in MF, we found that CTLA-4 is stimulated by phorbol myristate acetate/A23187 to a greater level when compared to normals. This defect was seen in the dominant clones of T cells. The increased CTLA-4 expression was significant between normal and MF, with a correlation between higher expression of CTLA-4 and a higher grade of MF. In a patient whose disease progressed, the CTLA-4 level increased. The abnormal level of CTLA-4 was confirmed at both the transcription and translation levels. Although MF is associated with a Th2 bias, Th1 cytokines IL-2 and IFN-gamma enhanced CTLA-4 expression, while IL-4 did not. These findings reveal an abnormal regulation of CTLA-4 expression in MF and show that PBMCs from patients with MF have properties that are divergent from those of normal T cells.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD
  • Antigens, Differentiation / analysis
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism*
  • CTLA-4 Antigen
  • Cytokines / metabolism
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycosis Fungoides / immunology*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Skin Neoplasms / immunology*
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Up-Regulation

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cytokines
  • RNA, Messenger