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T regulatory cells are a component of the immune system that suppress immune responses of other cells. This is an important "self-check" built into the immune system to prevent excessive reactions. Regulatory T cells come in many forms with the most well-understood being those that express CD4, CD25, and FOXP3 (CD4 + CD25 + regulatory T cells).
Foxp3 is a specific marker of natural T regulatory cells (nTregs, a lineage of T cells) and adaptive/induced T regulatory cells (a/iTregs), also identified by other less specific markers such as CD25 or CD45RB. [6] [7] [8] In animal studies, Tregs that express Foxp3 are critical in the transfer of immune tolerance, especially self-tolerance. [13]
CD4 is found on the surface of immune cells such as helper T cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 (after the OKT4 monoclonal antibody that reacted with it) before being named CD4 in 1984. [5] In humans, the CD4 protein is encoded by the CD4 gene. [6] [7]
Two major classes of CD4 + T reg cells have been described—FOXP3 + T reg cells and FOXP3 − T reg cells. Regulatory T cells can develop either during normal development in the thymus, and are then known as thymic Treg cells, or can be induced peripherally and are called peripherally derived Treg cells.
IPEX is caused by mutations in the gene FOXP3, which encodes transcription factor forkhead box P3 . FOXP3 is widely considered to be the master regulator of the regulatory T cell (Treg) lineage. [6] [7] FOXP3 mutation can lead to the dysfunction of CD4 + Tregs. In healthy people, Tregs maintain immune homeostasis. [8]
The T-Lymphocyte Helper/Suppressor Profile (Helper/Suppressor ratio, T4:T8 ratio, CD4:CD8 ratio) is a basic laboratory test in which the percentage of CD3-positive lymphocytes in the blood positive for CD4 (T helper cells) and CD8 (a class of regulatory T cells) are counted and compared.
In turn, this results in the T cell acquiring an activated phenotype seen by the up-regulation of surface markers CD25 +, CD44 +, CD62L low, CD69 + and may further differentiate into a memory T cell. Having adequate numbers of naive T cells is essential for the immune system to continuously respond to unfamiliar pathogens.
Suppressor-inducer T cells are a specific subset of CD4 + T helper cells that "induce" CD8 + cytotoxic T cells to become "suppressor" cells. [1] Suppressor T cells are also known as CD25 + –Foxp3 + regulatory T cells (nTregs), and reduce inflammation. [2] [3]