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Title: | CD6 modulates thymocyte selection and peripheral T cell homeostasis |
Author: | Orta Mascaró, Marc Consuegra-Fernández, Marta Carreras Margalef, Esther Roncagalli, Romain Carreras Sureda, Amado Alvarez, Pilar Girard, Laura Simões, Inês Martínez-Florensa, Mario Aranda, Fernando Merino, Ramón Martinez, Vanesa Gabriela Vicente García, Rubén, 1978- Merino, Jesús Sarukhan, Adelaida Malissen, Marie Malissen, Bernard Lozano Soto, Francisco |
Keywords: | Biologia molecular Receptors cel·lulars Homeòstasi Cèl·lules T Timus (Glàndula) Molecular biology Cell receptors Homeostasis T cells Thymus |
Issue Date: | 4-Jul-2016 |
Publisher: | Wiley |
Abstract: | The CD6 glycoprotein is a lymphocyte surface receptor putatively involved in T cell development and activation. CD6 facilitates adhesion between T cells and antigen-presenting cells through its interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), and physically associates with the T cell receptor (TCR) at the center of the immunological synapse. However, its precise role during thymocyte development and peripheral T cell immune responses remains to be defined. Here, we analyze the in vivo consequences of CD6 deficiency. CD6(-/-) thymi showed a reduction in both CD4(+) and CD8(+) single-positive subsets, and double-positive thymocytes exhibited increased Ca(2+) mobilization to TCR cross-linking in vitro. Bone marrow chimera experiments revealed a T cell-autonomous selective disadvantage of CD6(-/-) T cells during development. The analysis of TCR-transgenic mice (OT-I and Marilyn) confirmed that abnormal T cell selection events occur in the absence of CD6. CD6(-/-) mice displayed increased frequencies of antigen-experienced peripheral T cells generated under certain levels of TCR signal strength or co-stimulation, such as effector/memory (CD4(+)TEM and CD8(+)TCM) and regulatory (T reg) T cells. The suppressive activity of CD6(-/-) T reg cells was diminished, and CD6(-/-) mice presented an exacerbated autoimmune response to collagen. Collectively, these data indicate that CD6 modulates the threshold for thymocyte selection and the generation and/or function of several peripheral T cell subpopulations, including T reg cells. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1084/jem.20151785 |
It is part of: | The Journal of Trace Elements in Experimental Medicine, 2016, vol. 213, num. 8, p. 1387-1397 |
URI: | http://hdl.handle.net/2445/107636 |
Related resource: | https://doi.org/10.1084/jem.20151785 |
ISSN: | 0896-548X |
Appears in Collections: | Articles publicats en revistes (Biomedicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Publicacions de projectes de recerca finançats per la UE |
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667668.pdf | 5.97 MB | Adobe PDF | View/Open |
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