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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, Ines
Martínez-Florensa, Mario
Aranda, Fernando
Merino, Ramón
Martínez, Vanesa Gabriela
Vicente, Rubén
Merino, Jesús
Sarukhan, Adelaida
Malissen, Marie
Malissen, Bernard
Lozano Soto, Francisco
Keywords: Biologia molecular
Receptors cel·lulars
Cèl·lules T
Timus (Glàndula)
Molecular biology
Cell receptors
T cells
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:
It is part of: The Journal of Trace Elements in Experimental Medicine, 2016, vol. 213, num. 8, p. 1387-1397
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ISSN: 0896-548X
Appears in Collections:Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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