Going both ways: immune regulation via CD1d-dependent NKT cells

Going both ways: immune regulation via CD1d-dependent NKT cells

November 2004 | Dale I. Godfrey and Mitchell Kronenberg
NKT cells are a unique subset of T lymphocytes that recognize glycolipid antigens presented by CD1d, unlike conventional T cells that recognize peptide antigens. They can both promote and suppress immune responses by secreting Th1, Th2, or regulatory cytokines. This review discusses their diverse roles in immune regulation, including their ability to suppress or enhance immunity, and their potential as a novel immunotherapy. NKT cells are defined by their invariant TCR α chain (Va14-Ja18 in mice, Vα24-Ja18 in humans) and their ability to recognize CD1d-bound glycolipids. They are found in various tissues, with the highest frequency in the liver. They are also present in humans, though at lower frequencies than in mice. NKT cells can be divided into CD4+ and CD4- subsets, with some expressing CD8 in humans and monkeys. NKT cells are potent producers of immunosuppressive cytokines such as IL-4, IL-10, and IL-13, which can suppress cell-mediated immune responses. They have been shown to mediate allograft tolerance and suppress autoimmune diseases like type 1 diabetes and experimental autoimmune encephalomyelitis (EAE). However, they can also promote autoimmunity in certain contexts, highlighting their dual role. In cancer, NKT cells can promote tumor rejection by producing IFN-γ and other cytokines, and they have been tested in clinical trials with promising results. They also play a role in host defense against infections by producing IFN-γ and other cytokines, and their recognition of microbial glycolipids can contribute to immune responses. NKT cells are involved in allergic and inflammatory responses, and their role in human airway hyperresponsiveness is being studied. They can act as regulators, influencing immune responses through cytokine production and interactions with other immune cells. The dual functionality of NKT cells, capable of both promoting and suppressing immune responses, is influenced by factors such as the type of signals they receive, the TCR stimulation, and the microenvironment. Understanding these factors is crucial for harnessing NKT cells in immunotherapy. Future research aims to better understand NKT cell subsets and their regulation, which could lead to more effective therapeutic strategies.NKT cells are a unique subset of T lymphocytes that recognize glycolipid antigens presented by CD1d, unlike conventional T cells that recognize peptide antigens. They can both promote and suppress immune responses by secreting Th1, Th2, or regulatory cytokines. This review discusses their diverse roles in immune regulation, including their ability to suppress or enhance immunity, and their potential as a novel immunotherapy. NKT cells are defined by their invariant TCR α chain (Va14-Ja18 in mice, Vα24-Ja18 in humans) and their ability to recognize CD1d-bound glycolipids. They are found in various tissues, with the highest frequency in the liver. They are also present in humans, though at lower frequencies than in mice. NKT cells can be divided into CD4+ and CD4- subsets, with some expressing CD8 in humans and monkeys. NKT cells are potent producers of immunosuppressive cytokines such as IL-4, IL-10, and IL-13, which can suppress cell-mediated immune responses. They have been shown to mediate allograft tolerance and suppress autoimmune diseases like type 1 diabetes and experimental autoimmune encephalomyelitis (EAE). However, they can also promote autoimmunity in certain contexts, highlighting their dual role. In cancer, NKT cells can promote tumor rejection by producing IFN-γ and other cytokines, and they have been tested in clinical trials with promising results. They also play a role in host defense against infections by producing IFN-γ and other cytokines, and their recognition of microbial glycolipids can contribute to immune responses. NKT cells are involved in allergic and inflammatory responses, and their role in human airway hyperresponsiveness is being studied. They can act as regulators, influencing immune responses through cytokine production and interactions with other immune cells. The dual functionality of NKT cells, capable of both promoting and suppressing immune responses, is influenced by factors such as the type of signals they receive, the TCR stimulation, and the microenvironment. Understanding these factors is crucial for harnessing NKT cells in immunotherapy. Future research aims to better understand NKT cell subsets and their regulation, which could lead to more effective therapeutic strategies.
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