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CD6 modulates thymocyte selection and peripheral T cell homeostasis

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

Authorship

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

MARTÍNEZ, VANESA-GABRIELA

VICENTE, RUBÉN

SARUKHAN, ADELAIDA

MARISSEN, MARIE

MALISSEN, BERNARD

LOZANO, FRANCISCO