Membrane expression of NK receptors CD160 and CD158k contributes to delineate a unique CD4+ T-lymphocyte subset in normal and mycosis fungoides skin

Cytometry A. 2014 Oct;85(10):869-82. doi: 10.1002/cyto.a.22512. Epub 2014 Jul 18.

Abstract

CD160 is a GPI-anchored Ig-like receptor identified by the BY55 mAb on human circulating CD56dim+ NK cells and TCRγδ lymphocytes. In addition, while most intestinal T lymphocytes express it, only a minor circulating CD4+ or CD8+ T lymphocyte subset is CD160+. Here we describe a population of CD4+ CD160+ human blood T lymphocytes of circulating cutaneous T cells. These rare T lymphocytes represent 2.1 ± 1.9% of the circulating CD3+ CD4+ T cells, coexpress CD8αα, CD244, and perforin but lack CD28 expression, a phenotype corresponding to effector memory cytotoxic T-lymphocytes. Functional studies further confirmed their cytotoxic potential. These cells lack αEβ7 integrin and CCR7 expression but do express skin-addressing molecules CLA, and CCR4. In normal human skin, CD4+ CD160+ cells represent 34.6 ± 14.7% of the CD4+ T lymphocytes extracted by collagenase treatment. These T cells coexpress CLA (81 ± 13.6%), CCR4 (62.3 ± 15.9%), and some CD8αα (19.6 ± 13%) or CCR7 (24.4 ± 11.7%) expression. Cutaneous T-cell lymphoma cells express the natural killer receptor KIR3DL2 (CD158k) used as a tumor marker. Not only we confirmed the expression of this marker in the blood and/or skin of mycosis fungoides patients but we also show for the first time CD158k expression (often associated with CD160) on cutaneous CD4+ T cells from healthy individuals (25.3 ± 15%). Therefore, CD4+ CD160+ T cells expressing CD158k might represent specialized cutaneous lymphocytes devoted to immune surveillance, from which could originate cutaneous T-cell lymphomas such as mycosis fungoides.

Keywords: BY55; CD158k; CD160; KIR3DL2; mycosis fungoides; skin lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Membrane / metabolism
  • Female
  • Flow Cytometry / methods
  • GPI-Linked Proteins / biosynthesis
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Killer Cells, Natural / metabolism*
  • Male
  • Mycosis Fungoides / diagnosis
  • Mycosis Fungoides / metabolism*
  • Receptors, Immunologic / biosynthesis*
  • Receptors, KIR2DL2 / biosynthesis*
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / metabolism*
  • T-Lymphocyte Subsets / metabolism

Substances

  • Antigens, CD
  • CD160 protein, human
  • GPI-Linked Proteins
  • KIR2DL2 protein, human
  • Receptors, Immunologic
  • Receptors, KIR2DL2