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dc.contributor.author | Orta Mascaró, Marc |
---|---|
dc.contributor.author | Consuegra Fernández, Marta |
dc.contributor.author | Carreras Margalef, Esther |
dc.contributor.author | Roncagalli, Romain |
dc.contributor.author | Carreras Sureda, Amado |
dc.contributor.author | Alvarez, Pilar |
dc.contributor.author | Girard, Laura |
dc.contributor.author | Simões, Inês |
dc.contributor.author | Martínez-Florensa, Mario |
dc.contributor.author | Aranda, Fernando |
dc.contributor.author | Merino, Ramón |
dc.contributor.author | Martinez, Vanesa Gabriela |
dc.contributor.author | Vicente García, Rubén, 1978- |
dc.contributor.author | Merino, Jesús |
dc.contributor.author | Sarukhan, Adelaida |
dc.contributor.author | Malissen, Marie |
dc.contributor.author | Malissen, Bernard |
dc.contributor.author | Lozano Soto, Francisco |
dc.date | 2017-03-01T15:47:43Z |
dc.date | 2017-07-25T22:01:25Z |
dc.date | 2016-07-04 |
dc.date | 2017-03-01T15:47:43Z |
dc.identifier | 0896-548X |
dc.identifier | 667668 |
dc.identifier | 27377588 |
dc.identifier.uri | http://hdl.handle.net/2445/107636 |
dc.description | 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. |
dc.format | 11 p. |
dc.format | application/pdf |
dc.language | eng |
dc.publisher | Wiley |
dc.relation | Versió postprint del document publicat a: https://doi.org/10.1084/jem.20151785 |
dc.relation | The Journal of Trace Elements in Experimental Medicine, 2016, vol. 213, num. 8, p. 1387-1397 |
dc.relation | https://doi.org/10.1084/jem.20151785 |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/229673/EU//BIOTRACK |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/322465/EU//INTEGRATE |
dc.rights | (c) Wiley, 2016 |
dc.rights | info:eu-repo/semantics/openAccess |
dc.subject | Biologia molecular |
dc.subject | Receptors cel·lulars |
dc.subject | Homeòstasi |
dc.subject | Cèl·lules T |
dc.subject | Timus (Glàndula) |
dc.subject | Molecular biology |
dc.subject | Cell receptors |
dc.subject | Homeostasis |
dc.subject | T cells |
dc.subject | Thymus |
dc.title | CD6 modulates thymocyte selection and peripheral T cell homeostasis |
dc.type | info:eu-repo/semantics/article |
dc.type | info:eu-repo/semantics/acceptedVersion |