Sezary Syndrome Cells Unlike Normal Circulating T Lymphocytes Fail to Migrate Following Engagement of NT1 Receptor

• Published in: Journal of investigative dermatology Vol. 122; no. 1; pp. 111 - 118
• Main Authors: Magazin, Marilyn, Chalon, Pascale, Culouscou, Jean-Michel, Ferrara, Pascual, Poszepczynska-Guigné, Ewa, Bagot, Martine, Boumsell, Laurence, Pruvost, Christelle, Bensussan, Armand
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01-01-2004; Nature Publishing; Elsevier Limited
• Subjects: Actins - metabolism; Biological and medical sciences; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; chemotaxis; Chemotaxis - immunology; cutaneous T cell lymphoma; Dermatology; Enzyme Inhibitors - pharmacology; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Gene Expression - immunology; Hematologic and hematopoietic diseases; Humans; Jurkat Cells; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Neurokinin-1 Receptor Antagonists; neurotensin; Neurotensin - pharmacology; neurotensin receptors; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Pyrazoles - pharmacology; Quinolines - pharmacology; Receptors, Neurokinin-1 - genetics; Receptors, Neurokinin-1 - metabolism; Sezary cell; Sezary Syndrome - immunology; Sezary Syndrome - pathology; neurotensin receptors; neurotensin; Sezary cell; cutaneous T cell lymphoma; chemotaxis; Skin disease; Dermatology; Malignant hemopathy; Non Hodgkin lymphoma; Peripheral T cell lymphoma; neurotensin/neurotensin receptors/cutaneous T cell lymphoma/Sezary cell/chemotaxis; Chronic; Cutaneous hematologic disease; Sezary syndrome; Lymphoproliferative syndrome; T-Lymphocyte; Biological receptor
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1046/j.0022-202X.2003.22131.x

Circulating malignant Sezary cells are a clonal proliferation of CD4+CD45RO+ T lymphocytes primarily involving the skin. To study the biology of these malignant T lymphocytes, we tested their ability to migrate in chemotaxis assays. Previously, we had shown that the neuropeptide neurotensin (NT) binds to freshly isolated Sezary malignant cells and induces through NT1 receptors the cell migration of the cutaneous T cell lymphoma cell line Cou-L. Here, we report that peripheral blood Sezary cells as well as the Sezary cell line Pno fail to migrate in response to neurotensin although they are capable of migrating to the chemokine stromal-cell-derived factor 1α. This is in contrast with normal circulating CD4+ or CD8+ lymphocytes, which respond to both types of chemoattractants except after ex vivo short-time anti-CD3 monoclonal antibody activation, which abrogates the neurotensin-induced lymphocyte migration. Furthermore, we demonstrate that neurotensin-responsive T lymphocytes express the functional NT1 receptor responsible for chemotaxis. In these cells, but not in Sezary cells, neurotensin induces recruitment of phosphatidylinositol-3 kinase, and redistribution of phosphorylated cytoplasmic tyrosine kinase focal adhesion kinase and filamentous actin. Taken together, these results, which show functional distinctions between normal circulating lymphocytes and Sezary syndrome cells, contribute to further understanding of the physiopathology of these atypical cells.