title: 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.
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain.
authors.forename: Marc
authors.identifier: 0000-0003-4923-2083
authors.initials: M
authors.lastname: Orta-Mascaró
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Consuegra-Fernández
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain.
authors.forename: Esther
authors.identifier: 0000-0001-9184-8266
authors.initials: E
authors.lastname: Carreras
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale, U1104, Centre National de la Recherche Scientifique UMR7280, 13402 Marseille, France.
authors.forename: Romain
authors.identifier: 0000-0001-7554-0552
authors.initials: R
authors.lastname: Roncagalli
authors.affiliation: Universitat Pompeu Fabra, 08002 Barcelona, Spain.
authors.forename: Amado
authors.identifier: 0000-0002-9032-5639
authors.initials: A
authors.lastname: Carreras-Sureda
authors.affiliation: Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas-Universidad de Cantabria, 39005 Santander, Spain.
authors.forename: Pilar
authors.identifier: 0000-0002-6331-0933
authors.initials: P
authors.lastname: Alvarez
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale, U1104, Centre National de la Recherche Scientifique UMR7280, 13402 Marseille, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Girard
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain.
authors.forename: Inês
authors.identifier: 0000-0003-1730-7263
authors.initials: I
authors.lastname: Simões
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain.
authors.forename: Mario
authors.identifier: 0000-0002-5673-9803
authors.initials: M
authors.lastname: Martínez-Florensa
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Aranda
authors.affiliation: Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas-Universidad de Cantabria, 39005 Santander, Spain.
authors.forename: Ramón
authors.identifier: 0000-0002-5306-0635
authors.initials: R
authors.lastname: Merino
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain.
authors.forename: Vanesa-Gabriela
authors.initials: VG
authors.lastname: Martínez
authors.affiliation: Universitat Pompeu Fabra, 08002 Barcelona, Spain.
authors.forename: Rubén
authors.identifier: 0000-0003-0401-4808
authors.initials: R
authors.lastname: Vicente
authors.affiliation: Departmento de Biología Molecular, Universidad de Cantabria, Instituto de Investigación Sanitaria Valdecilla, 39011 Santander, Spain.
authors.forename: Jesús
authors.identifier: 0000-0003-3476-1150
authors.initials: J
authors.lastname: Merino
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, 75654 Paris, France.
authors.forename: Adelaida
authors.initials: A
authors.lastname: Sarukhan
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale, U1104, Centre National de la Recherche Scientifique UMR7280, 13402 Marseille, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Malissen
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Institut National de la Santé et de la Recherche Médicale, U1104, Centre National de la Recherche Scientifique UMR7280, 13402 Marseille, France.
authors.forename: Bernard
authors.identifier: 0000-0003-1340-9342
authors.initials: B
authors.lastname: Malissen
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain Servei d'Immunologia, Hospital Clínic de Barcelona, 08036 Barcelona, Spain Departament de Biologia Cellular, Immunologia i Neurociències, Universitat de Barcelona, 08007 Barcelona, Spain flozano@clinic.ub.es.
authors.forename: Francisco
authors.identifier: 0000-0003-1119-4368
authors.initials: F
authors.lastname: Lozano
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D054992:Immunological Synapses / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011946:Receptors, Antigen / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D060168:Thymocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D011946:Receptors, Antigen