# CD3 + CD4 - CD8 - (Double-Negative) T Cells in Inflammation, Immune Disorders and Cancer

Review · Wu Z, Zheng Y, Sheng J, Han Y, Yang Y, Pan H, Yao J

- Archive id: doi:10.3389/fimmu.2022.816005
- Published: 2022-02-10
- Venue: Frontiers in immunology
- DOI: https://doi.org/10.3389/fimmu.2022.816005
- PMID: 35222392
- PMCID: PMC8866817
- Citations: 224
- Source URL: https://doi.org/10.3389/fimmu.2022.816005
- PDF: https://europepmc.org/articles/PMC8866817/pdf
- Provenance: europepmc

## Abstract

The crucial role of CD4 + and CD8 + T cells in shaping and controlling immune responses during immune disease and cancer development has been well established and used to achieve marked clinical benefits. CD3 + CD4 - CD8 - double-negative (DN) T cells, although constituting a rare subset of peripheral T cells, are gaining interest for their roles in inflammation, immune disease and cancer. Herein, we comprehensively review the origin, distribution and functions of this unique T cell subgroup. First, we focused on characterizing multifunctional DN T cells in various immune responses. DN regulatory T cells have the capacity to prevent graft-versus-host disease and have therapeutic value for autoimmune disease. T helper-like DN T cells protect against or promote inflammation and virus infection depending on the specific settings and promote certain autoimmune disease. Notably, we clarified the role of DN tumor-infiltrating lymphocytes and outlined the potential for malignant proliferation of DN T cells. Finally, we reviewed the recent advances in the applications of DN T cell-based therapy for cancer. In conclusion, a better understanding of the heterogeneity and functions of DN T cells may help to develop DN T cells as a potential therapeutic tool for inflammation, immune disorders and cancer.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Cancer Immunotherapy](https://space-kitty.com/topics/cancer-immunotherapy)

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