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

• Published in: Frontiers in immunology Vol. 13; p. 816005
• Main Authors: Wu, Zhiheng, Zheng, Yu, Sheng, Jin, Han, Yicheng, Yang, Yanyan, Pan, Hongming, Yao, Junlin
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 10.02.2022
• Subjects: Autoimmune Diseases - therapy; cancer; CD8 Antigens; CD8-Positive T-Lymphocytes; double-negative T cell; Graft vs Host Disease; helper function; Humans; immune disorders; Immunology; immunoregulation; Inflammation; Neoplasms - therapy; helper function; inflammation; immune disorders; immunotherapy; double-negative T cell; immunoregulation; cancer; tumor microenvironment
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.816005

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.