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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]
In addition to IPEX-like symptoms, CD25 deficiency increases susceptibility to viral infections [1] and possibly fungal and bacterial infections. As IL-2 is an important inducer of lymphocyte proliferation , the absence of highly sensitive IL-2 receptors may also significantly hinder activation and clonal expansion of CD8+ and CD4+ lymphocytes ...
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]
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] When there is a deleterious FOXP3 mutation, Tregs do not function properly and cause autoimmunity. [8] [9] IPEX onset usually ...
A thymocyte becomes a CD4 + cell by down-regulating expression of its CD8 cell surface receptors. If the cell does not lose its signal, it will continue downregulating CD8 and become a CD4 +, both CD8 + and CD4 + cells are now single positive cells. [11] This process does not filter for thymocytes that may cause autoimmunity. The potentially ...
Low CD4 + predicted greater likelihood of intensive care unit admission, and CD4 + cell count was the only parameter that predicted length of time for viral RNA clearance. [42] Despite the reduced levels of CD4 + , COVID-19 patients with severe disease had higher levels of T h 1 CD4 + cells than patients with moderate disease. [ 43 ]
The Scurfin protein, which regulates the development of CD4+CD25+ regulatory T cells, is encoded by FOXP3. [25] DNA-binding domain defects in IPEX are caused by mutations in the FOXP3 gene. [26] This disrupts regulatory T cells' regular function, triggering aberrant immune reactions that cause autoimmune symptoms like enteropathy. [27]