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Review
. 2021 Mar 1;33(2):163-172.
doi: 10.1097/BOR.0000000000000778.

Double-negative T cells in autoimmune diseases

Hao Li  1 , George C Tsokos
Affiliations
Review

Double-negative T cells in autoimmune diseases

Hao Li et al. Curr Opin Rheumatol. .

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.

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Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

Figures

Fig. 1.
Fig. 1.. Ontogeny of DN T cells.
a. Peripheral DNT cells derive directly from immature DN thymocytes or from DP thymocytes through the downregulation of both CD4 and CD8. b. Left: Activated CD8 T cells without proper apoptotic signals escape AICD and give rise to DNT cells. Right: Cytokine signal inputs help the conversion from CD8 T cells to DNT cells.
Fig. 2.
Fig. 2.. Therapeutic interventions targeting DNT cells
a. Regulate the conversion between DNT cells and CD8 T cells through epigenetic modulation. b. Eliminate DNT cells by adding missing signals for apoptosis. c. Regulate the conversion between DNT cells and CD8 T cells by reshaping the cytokine milieu. d. Inhibit DNT cell activation and expansion by targeting DNT cell metabolism.
See this image and copyright information in PMC

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