IMMUNOPATHOGENESIS AND TREATMENT OF AUTOIMMUNE DISEASES: Edited by George C. TsokosDouble-negative T cells in autoimmune diseasesLi, Hao; Tsokos, George C. Author Information Division of Rheumatology and Clinical Immunology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA Correspondence to Hao Li, MD, PhD, Harvard University, Boston 02115, MA, USA. E-mail: [email protected], [email protected] Current Opinion in Rheumatology 33(2):p 163-172, March 2021. | DOI: 10.1097/BOR.0000000000000778 Buy Metrics Abstract Purpose of review TCRαβ+CD4-CD8- double-negative T (DNT) cells, a principal subset of mature T lymphocytes, have been closely linked with autoimmune/inflammatory conditions. However, controversy persists regarding their ontogeny and function. Here, we present an overview on DNT cells in different autoimmune diseases to advance a deeper understanding of the contribution of this population to disease pathogenesis. Recent findings DNT cells have been characterized in various chronic inflammatory diseases and they have been proposed to display pathogenic or regulatory function. The tissue location of DNT cells and the effector cytokines they produce bespeak to their active involvement in chronic inflammatory diseases. Summary By producing various cytokines, expanded DNT cells in inflamed tissues contribute to the pathogenesis of a variety of autoimmune inflammatory diseases. However, it is unclear whether this population represents a stable lineage consisting of different subsets similar to CD4+ T helper cell subset. Better understanding of the possible heterogeneity and plasticity of DNT cells is needed to reveal interventional therapeutic opportunities. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.