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Chapter 31 : Regulatory T Cell (Treg) Assays: Repertoire, Functions, and Clinical Importance of Human Treg
Regulatory T cells (Treg) are a small subset (<5%) of circulating CD4+ T cells. Due to their ability to suppress functions of other lymphocytes, Treg are responsible for maintaining immune responses in balance. This system of immune checks and balances exists to protect us from autoimmune diseases, prevent tissue damage resulting from intense inflammatory responses induced by infectious or non-infectious injuries and to contain chronic inflammatory reactions that might promote tumor development (1). Treg seem to be capable of fulfilling all these functions, largely due to their plasticity, which allows them to readily adjust to conditions in the local microenvironment (2). Viewed in this context, Treg can be considered as a protective mechanism designed to limit inflammatory tissue damage, but also as a potentially dangerous suppressor of immune responses that benefit the host. For example, in chronic viral infections such as HIV-1 infections, Treg could either suppress excessive immune activation, thus benefiting the host, or limit antiviral immunity needed by the host to contain the infection. Today, the role of Treg in HIV-1 remains highly controversial (3). In cancer, Treg are emerging both as contributors to cancer progression, because of their ability to block anti-tumor immune responses, and also as inhibitors of cancer progression via their ability to suppress cancer-promoting inflammation (4). It is unclear whether the anti-inflammatory activity of Treg or their suppression of antitumor immunity contributes to disease outcome, and the mechanisms responsible for regulation of Treg functions remain unknown. Factors that govern Treg behavior in situ are being intensely investigated in various human diseases. An excess of Treg (e.g., in some cancers) or their numerical or functional deficiency (e.g., in autoimmune diseases) is associated with clinical symptoms and may predict outcome. For these reasons, measurements of Treg frequency and function in the circulation, and especially in tissues, are of great importance.