Functional expression of the calcitonin receptor by human T and B cells

• Published in: Human immunology 2009-09, Vol.70 (9), p.678-685
• Main Authors: Cafforio, Paola, De Matteo, Monica, Brunetti, Anna Elisabetta, Dammacco, Franco, Silvestris, Franco
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Calcium - metabolism; Calcium efflux; Calcium Signaling - immunology; CD69; Cell Proliferation; Cells, Cultured; Child; Child, Preschool; Chronic lymphocytic leukemia; Dose-Response Relationship, Immunologic; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - blood; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Multiple myeloma; Palatine Tonsil - pathology; PKC; Receptors, Calcitonin - genetics; Receptors, Calcitonin - immunology; Receptors, Calcitonin - metabolism; Salmon; Salmonidae; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2009.05.005

Abstract The calcitonin receptor (CTR) is a seven-transmembrane–domain G-protein–coupled receptor that regulates calcium metabolism and bone resorption by osteoclasts. Here we demonstrate that high levels are expressed by normal human T and B lymphocytes from tonsils and peripheral blood in relation to their activation status, as CTR+ T cells are prone to produce IFN-γ after TCR stimulation. The receptor is also highly expressed on B cells from chronic lymphocytic leukemia patients, thus suggesting a correlation between its expression, their proliferative extent as well as their memory, antigen-experienced phenotype. Moreover, we found that binding of the receptor with salmon calcitonin induces an increase of intracellular calcium2+ in peripheral lymphocytes. This effect is involved in several lymphocyte immune functions, as cytosolic calcium2+ levels regulate both cell proliferation and cytokine production. In our hands, the increase of calcium2+ levels by CTR binding with sCT induced a dose-dependent cell proliferation. We therefore suppose that expression of this functional receptor may contribute to the modulation of cytoplasmic calcium2+ levels needed to regulate T and B cell activation and perhaps other immune functions.