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

Abstract

CD160 is a GPI-anchored Ig-like receptor identified by the BY55 mAb on human circulating CD56 dim1 NK cells and TCRcd lymphocytes. In addition, while most intestinal T lymphocytes express it, only a minor circulating CD4 1 or CD8 1 T lymphocyte subset is CD160 1 . Here we describe a population of CD4 1 CD160 1 human blood T lymphocytes of circulating cutaneous T cells. These rare T lymphocytes represent 2.1 6 1.9% of the circulating CD3 1 CD4 1 T cells, coexpress CD8aa, CD244, and perforin but lack CD28 expression, a phenotype corresponding to effector memory cytotoxic Tlymphocytes. Functional studies further confirmed their cytotoxic potential. These cells lack aEb7 integrin and CCR7 expression but do express skin-addressing molecules CLA, and CCR4. In normal human skin, CD4 1 CD160 1 cells represent 34.6 6 14.7% of the CD4 1 T lymphocytes extracted by collagenase treatment. These T cells coexpress CLA (81 6 13.6%), CCR4 (62.3 6 15.9%), and some CD8aa (19.6 6 13%) or CCR7 (24.4 6 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 1 T cells from healthy individuals (25.3 6 15%). Therefore, CD4 1 CD160 1 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.

Innovative Treatment Concepts for Cutaneous T-Cell Lymphoma Based on Microenvironment Modulation

“…Aberrantly expressed KIR3DL2 has been described as a reliably expressed surface marker of MF and SS cells [44]. Its expression in healthy individuals is limited to natural killer (NK) cells and a small number of T cells.…”

Monoclonal Antibodies

“…KIRs are transmembrane glycoproteins normally expressed by NK cells and a small subset of T cells, but they are highly and constitutively expressed in CTCL. 60 A recent study reported the development of IPH4102, a humanized mAb that targets the immune receptor KIR3DL2. 61 Potent antitumor properties of IPH4102 were documented in allogeneic human CTCL cells and a mouse model of KIR3DL2(1) disease.…”

Innovative Behandlungskonzepte mit Modulation der Mikroumgebung beim kutanen T-Zell-Lymphom

“…Die aberrante Expression von KIR3DL2 ist als durchgängig vorhandener Oberflächenmarker von MF- und SS-Zellen beschrieben worden [44]. Physiologischerweise beschränkt sich die Expression auf natürliche Killerzellen (NK-Zellen) und einen kleinen Teil der T-Lymphozyten.…”