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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. © 2014 International Society for Advancement of Cytometry

SPECIFIC AIMSHuman γδ T lymphocytes activate their immune function upon TCR-mediated recognition of antigens not associated with MHC molecules. Because different nonpeptide phosphorylated antigens (phosphoantigens) are selectively recognized by γδ T cells, we clarified its molecular basis through the structure–function relationship of novel synthetic phosphoantigens.PRINCIPAL FINDINGSParadoxically, human γδ T cell-mediated recognition of phosphoantigens is highly specific and broadly cross-reactive. The relationship between structure and activity of several natural or synthetic phosphoantigens shows the importance of conformational determinants, but also reveals the critical role of the chemical reactivity of phosphoantigens. Phosphoepoxides and phosphohalohydrins are new synthetic phosphoantigens that were designed on this basis and constitute the most potent γδ cell-stimulating compounds so far. For optimal Vγ9Vδ2 T cell activation, both organic and phosphorylated moieties of these ligands undergo rapid...