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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/107636

CD6 modulates thymocyte selection and peripheral T cell homeostasis

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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.

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ORTA MASCARÓ, Marc, CONSUEGRA-FERNÁNDEZ, Marta, CARRERAS MARGALEF, Esther, RONCAGALLI, Romain, CARRERAS SUREDA, Amado, ÁLVAREZ, Pilar, GIRARD, Laura, SIMÕES, Inês, MARTÍNEZ-FLORENSA, Mario, ARANDA, Fernando, MERINO, Ramón, MARTINEZ, Vanesa gabriela, VICENTE GARCÍA, Rubén, MERINO, Jesús, SARUKHAN, Adelaida, MALISSEN, Marie, MALISSEN, Bernard, LOZANO SOTO, Francisco. CD6 modulates thymocyte selection and peripheral T cell homeostasis. _The Journal of Trace Elements in Experimental Medicine_. 2016. Vol. 213, núm. 8, pàgs. 1387-1397. [consulta: 20 de gener de 2026]. ISSN: 0896-548X. [Disponible a: https://hdl.handle.net/2445/107636]

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