CD8 + CD161 + T-Cells: Cytotoxic Memory Cells With High Therapeutic Potential

• Published in: Frontiers in immunology 2021-02, Vol.11, p.613204-613204
• Main Authors: Konduri, Vanaja, Oyewole-Said, Damilola, Vazquez-Perez, Jonathan, Weldon, Scott A, Halpert, Matthew M, Levitt, Jonathan M, Decker, William K
• Format: Article
• Language: English
• Subjects: CD161; effector memory; Immunology; KLRB1; T-cell; TH1 polarization
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.613204

NK1.1 and its human homolog CD161 are expressed on NK cells, subsets of CD4 and CD8 T cells, and NKT cells. While the expression of NK1.1 is thought to be inhibitory to NK cell function, it is reported to play both costimulatory and coinhibitory roles in T-cells. CD161 has been extensively studied and characterized on subsets of T-cells that are MR1-restricted, IL-17 producing CD4 (T 17 MAIT cells) and CD8 T cells (Tc17 cells). Non-MAIT, MR1-independent CD161-expressing T-cells also exist and are characterized as generally effector memory cells with a stem cell like phenotype. Gene expression analysis of this enigmatic subset indicates a significant enhancement in the expression of cytotoxic granzyme molecules and innate like stress receptors in CD8 NK1.1 /CD8 CD161 cells in comparison to CD8 cells that do not express NK1.1 or CD161. First identified and studied in the context of viral infection, the role of CD8 CD161 T-cells, especially in the context of tumor immunology, is still poorly understood. In this review, the functional characteristics of the CD161-expressing CD8 T cell subset with respect to gene expression profile, cytotoxicity, and tissue homing properties are discussed, and application of this subset to immune responses against infectious disease and cancer is considered.