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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.
Fuente: Journal of Experimental Medicine, 2016, 213(8):1387-1397
Publisher: Rockefeller University Press
Year of publication: 2016
No. of pages: 11
Publication type: Article
DOI: 10.1084/jem.20151785
ISSN: 0022-1007,1540-9538
Publication Url: https://doi.org/10.1084/jem.20151785
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ORTA MASCARÓ, MARC
CONSUEGRA FERNÁNDEZ, MARTA
CARRERAS, ESTHER
RONCAGALLI, ROMAIN
CARRERAS SUREDA, AMADO
PILAR ALVAREZ SAINZ DE LA MAZA
GIRARD, LAURA
SIMOES, INÉS
MARTÍNEZ FLORENSA, MARIO
ARANDA, FERNANDO
RAMON MERINO PEREZ
MARTÍNEZ, VANESA-GABRIELA
VICENTE, RUBÉN
JESUS MERINO PEREZ
SARUKHAN, ADELAIDA
MARISSEN, MARIE
MALISSEN, BERNARD
LOZANO, FRANCISCO
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