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CD6 modulates thymocyte selection and peripheral T cell homeostasis

AuthorsOrta-Mascaró, Marc; Álvarez, Pilar; Merino, Ramón ; Martínez, Vanesa G.; Merino, Jesús; Lozano, Francisco
Issue Date2016
PublisherRockefeller University Press
CitationJournal of Experimental Medicine 213(8): 1387-1397 (2016)
AbstractThe 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.
DescriptionOrta-Mascaró et al.
Publisher version (URL)https://doi.org/10.1084/jem.20151785
Identifiersdoi: 10.1084/jem.20151785
e-issn: 1540-9538
issn: 0022-1007
Appears in Collections:(IBBTEC) Artículos
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