Immunome Research
Open Access

Activation and Effector Functions of Natural Killer T Cells in Immune Surveillance

Vasileios Lagopoulos^{* *}Correspondence: Vasileios Lagopoulos, Department of Medicine, Aristotle University, Thessaloniki, Greece, Email:

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About the Study

The immune system is a complex network of cells and molecules that work together to protect the body from pathogens and foreign invaders. Among the various components of the immune system, Natural Killer T (NKT) cells have emerged as a crucial player in immune surveillance. These unique cells possess both innate and adaptive immune features, enabling them to recognize and respond to a wide range of antigens.

Development of NKT cells

Natural killer T cells are a subset of lymphocytes that express markers characteristic of both Natural Killer (NK) cells and T cells. They originate from common lymphoid progenitors in the bone marrow and undergo a distinct developmental pathway compared to conventional T cells. The development of NKT cells is mediated by the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF), which is essential for their lineage commitment and functional maturation. During development, NKT cells acquire a semi-invariant T Cell Receptor (TCR) that recognizes glycolipid antigens presented by the non-classical Major Histocompatibility Complex (MHC) class I molecule, CD1d.

Activation of NKT cells

Upon encounter with Antigen-Presenting Cells (APCs) such as dendritic cells, NKT cells can be activated through their TCR in conjunction with co-stimulatory signals. The semi-invariant TCR of NKT cells enables them to recognize a diverse array of glycolipid antigens derived from self or microbial sources. Additionally, NKT cells can be activated in a TCR-independent manner through cytokine stimulation, particularly by Interleukin-12 (IL-12) and IL-18 produced during infection or inflammation. Once activated, NKT cells rapidly produce a variety of cytokines, including Interferon-Gamma (IFN-γ), Tumor Necrosis Factor-Alpha (TNF-α), and Interleukin-4 (IL-4), which orchestrate immune responses against pathogens and modulate the activity of other immune cells.

Effector functions of NKT cells

Natural killer T cells exhibit potent effector functions that contribute to immune surveillance and host defense against infections and cancer. Through their ability to rapidly produce cytokines, NKT cells can directly kill infected or malignant cells, promote the activation and maturation of dendritic cells, and regulate the function of other immune cells, including T cells, B cells, and NK cells. Moreover, NKT cells play a critical role in bridging innate and adaptive immunity by modulating the initiation and magnitude of antigen-specific T and B cell responses. By virtue of their unique effector functions, NKT cells exert broad immunoregulatory effects that influence the outcome of immune responses in diverse pathological conditions.

Role of NKT cells in disease

The importance of NKT cells in immune surveillance is underscored by their involvement in various disease settings. Dysregulation of NKT cell function has been implicated in the pathogenesis of autoimmune diseases, such as multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, where aberrant NKT cell activation or cytokine production can exacerbate tissue inflammation and damage. Conversely, NKT cells have been shown to possess immunoregulatory properties that can ameliorate autoimmune responses and promote tissue repair in certain contexts. Furthermore, NKT cells play a dual role in cancer immunity, exhibiting both pro-tumorigenic and antitumorigenic activities depending on the tumor microenvironment and stage of disease progression. Harnessing the therapeutic potential of NKT cells in cancer immunotherapy holds promise for enhancing anti-tumor immune responses and improving clinical outcomes.

Natural killer T cells represent a unique immune cell population that bridges innate and adaptive immunity, playing a critical role in immune surveillance and host defense against infections, cancer, and autoimmune diseases. Their ability to rapidly respond to a diverse array of antigens and modulate immune responses makes them attractive targets for therapeutic intervention in various disease conditions.