Publicaciones científicas
CD6 modulates thymocyte selection and peripheral T cell homeostasis
Marc Orta-Mascaró 1, Marta Consuegra-Fernández 1, Esther Carreras 1, Romain Roncagalli 2, Amado Carreras-Sureda 3, Pilar Alvarez 4, Laura Girard 2, Inês Simões 1, Mario Martínez-Florensa 1, Fernando Aranda 1, Ramón Merino 4, Vanesa-Gabriela Martínez 1, Rubén Vicente 3, Jesús Merino 5, Adelaida Sarukhan 6, Marie Malissen 2, Bernard Malissen 2, Francisco Lozano 7
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.
CITA DEL ARTÍCULO J Exp Med. 2016 Jul 25;213(8):1387-97. doi: 10.1084/jem.20151785. Epub 2016 Jul 4.
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