title: Pro-inflammatory self-reactive T cells are found within murine TCR-αβ(+) CD4(-) CD8(-) PD-1(+) cells.
abstract: TCR-αβ(+) double negative (DN) T cells (CD3(+) TCR-αβ(+) CD4(-) CD8(-) NK1.1(-) CD49b(-) ) represent a minor heterogeneous population in healthy humans and mice. These cells have been ascribed pro-inflammatory and regulatory capacities and are known to expand during the course of several autoimmune diseases. Importantly, previous studies have shown that self-reactive CD8(+) T cells become DN after activation by self-antigens, suggesting that self-reactive T cells may exist within the DN T-cell population. Here, we demonstrate that programmed cell death 1 (PD-1) expression in unmanipulated mice identifies a subset of DN T cells with expression of activation-associated markers and a phenotype that strongly suggests they are derived from self-reactive CD8(+) cells. We also found that, within DN T cells, the PD-1(+) subset generates the majority of pro-inflammatory cytokines. Finally, using a TCR-activation reporter mouse (Nur77-GFP), we confirmed that in the steady-state PD-1(+) DN T cells engage endogenous antigens in healthy mice. In conclusion, we provide evidence that indicates that the PD-1(+) fraction of DN T cells represents self-reactive cells.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Departamento de Inmunología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.|Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: Noé
authors.initials: N
authors.lastname: Rodríguez-Rodríguez
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Sokratis A
authors.initials: SA
authors.lastname: Apostolidis
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Fitzgerald
authors.affiliation: The Department of Microbiology and Immunology, The University of Melbourne and The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
authors.forename: Bronwyn S
authors.initials: BS
authors.lastname: Meehan
authors.affiliation: The Department of Microbiology and Immunology, The University of Melbourne and The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Corbett
authors.affiliation: Departamento de Inmunología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Martín-Villa
authors.affiliation: The Department of Microbiology and Immunology, The University of Melbourne and The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: José C
authors.initials: JC
authors.lastname: Crispín
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D015551:Autoimmunity; D015415:Biomarkers; D015704:CD4 Antigens / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D015415:Biomarkers; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D061026:Programmed Cell Death 1 Receptor; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: Autoimmunity ⋅ DN T cells ⋅ IL-17 ⋅ Nur77-GFP mice ⋅ PD-1