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The uniqueness of iNKT cells: Why do these cells respond so quickly to danger signals?
NKT cells, also known as natural killer T cells, are a heterogeneous group that has the characteristics of both T cells and natural killer cells. These cells primarily recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that can bind self and foreign lipids and glycolipids. Although NKT cells account for only about 1% of peripheral blood T cells, they play a vital role in the immune system.
NKT cells were first described in mice due to their expression of the natural killer cell-associated marker NK1.1, and this term is now generally accepted to refer to CD1d-restricted T cells present in mice and humans.
The molecular characteristics of these NKT cells distinguish them from general αβ T cells. In contrast, their T cell receptors (TCRs) have lower diversity, divided into "type 1" fixed NKT cells and "type 2" CD1d-restricted T cells. One of the functions of these cells is to recognize lipids and glycolipids presented by the CD1d molecule, an ability that is crucial for fighting pathogens such as Mycobacterium tuberculosis.
Classification of NKT cells
Based on the characteristics expressed, NKT cells are usually divided into three main categories, the best known of which are "immobilized NKT cells" (iNKT cells). These cells can quickly activate when stimulated by danger signals, thereby initiating a series of immune responses. For example, after being influenced by proinflammatory cytokines, they can effectively perform different effector functions, including NK transactivation, T cell activation, B cell activation, etc.
The importance of iNKT cellsThe recognition of lipid antigens by iNKT cells relies on their invariant TCRs, which are highly conserved between humans and mice, especially the Va24-Ja18 pairing Vb11.
The development of iNKT cells normally occurs in the thymus and they are subsequently distributed throughout the body, with the highest number found in the liver. Additionally, they play an important role in several diseases, including autoimmune diseases. Studies have shown that the number of iNKT cells is reduced in the peripheral blood of patients with some autoimmune diseases, raising questions about whether they are the root cause of the disease.
Function of NKT cells
Once activated, NKT cells can secrete a variety of cytokines and chemical factors, such as large amounts of interferon-γ (IFN-γ), IL-4, and granulocyte stimulating factor. The effects of these cells not only effectively protect against microbial infections, but also enhance humoral immunity and contribute to the action of B cells. In addition, they have potential implications for how well vaccines work.
Clinical significanceThe dysfunction or loss of NKT cells is closely related to the development of various immune-related diseases such as diabetes, atherosclerosis and cancer.
The potential of NKT cells is not only reflected in their rapid regulation of immune responses, but their function or loss may lead to many health problems, including chronic inflammation and autoimmune diseases. Studies have shown that NKT cells may play an important role in the progression of asthma. Although NKT cells are relatively small in number, their unique abilities make them important immune regulators.
In experiments, the response pattern of NKT cells has a significant impact on the development of the immune system. This is critical because it may impact patients’ treatment options and disease management. While we wait for clinical applications, can we maximize the potential of NKT cells and make them the key to future vaccine research and therapy development?
