2024-03-29T15:50:02Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1643082020-12-13T09:20:37Zcom_10261_3284com_10261_1col_10261_3285
DIGITAL.CSIC
author
Orta-Mascaró, Marc
author
Álvarez, Pilar
author
Merino, Ramón
author
Martínez, Vanesa G.
author
Merino, Jesús
author
Lozano, Francisco
funder
European Research Council
funder
Fundação para a Ciência e a Tecnologia (Portugal)
funder
National Institutes of Health (US)
funder
Institut National de la Santé et de la Recherche Médicale (France)
funder
Centre National de la Recherche Scientifique (France)
funder
Fibrostatin
funder
European Commission
funder
Ministerio de Economía y Competitividad (España)
funder
Fundació La Marató de TV3
funder
Worldwide Cancer Research
2018-04-27T12:33:59Z
2018-04-27T12:33:59Z
2016
Journal of Experimental Medicine 213(8): 1387-1397 (2016)
http://hdl.handle.net/10261/164308
10.1084/jem.20151785
http://dx.doi.org/10.13039/501100007287http://dx.doi.org/10.13039/501100000780http://dx.doi.org/10.13039/501100004794http://dx.doi.org/10.13039/501100001677http://dx.doi.org/10.13039/100000002http://dx.doi.org/10.13039/501100000781http://dx.doi.org/10.13039/100008666http://dx.doi.org/10.13039/501100003329http://dx.doi.org/10.13039/501100001871
27377588
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/ALC AM (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 Ca2 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 (CD4TEM and CD8TCM) 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.
eng
openAccess
CD6 modulates thymocyte selection and peripheral T cell homeostasis
artículo
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URL
https://digital.csic.es/bitstream/10261/164308/1/CD6modulate.pdf
File
MD5
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application/pdf
CD6modulate.pdf