Foxp3+ and CD4CD25+ T cells and its Clinical Relation to Type 1 Diabetes

Abstract

T regulatory (Tr) cells are a distinct population of T cells which modulate T helper Th1 and Th2 mediated immuno-responses and maintain immunological homeostasis." Therefore, there are two subsets of T reg Tr type 1(Tr1) and CD4CD25 T lymphocytes the well described subsets of  CD4+ Tr cells. CD4+CD25+ T lymphocytes are naturally occurring CD4 T lymphocytes" that express CD marker number 25 that arises from thymus and seeds into periphery, creating a cohort of cells with profound T-cells immunesuppressive qualities." Cells that does not express CD4CD25 (CD4-CD25-) T-lymphocytes are detected in human blood and can suppress proliferation and production of cytokines from T lymphocytes that does not express CD4CD4 (CD4-CD4-)T lymphocyte in vitro in which a cell could not attached to another one in a contact dependent manner ( Jonuleit et. al,2001; Dieckmann et. al,2001; Levings et. al.,2001; Ng et. al.,2001 and Piccirillo et.al. 2001).                                                                                  

Tr1 and CD4+CD25+ T lymphocytes are similar to each other in biological characteristics like slow or absence of cell division in vitro, and suppress capacity in vivo and in vitro. Activity of Tr1 subsets is by secretion of "IL-10 and (TGF-β)", while suppressive mechanism of CD4+CD25+ T lymphocytes have not well explained. CD4+CD25+ T- lymphocytes  have been largely studied in autoimmune diseases, whereas Tr1 cells have been widely investigated in transplantation, chronic infectious diseases and allergy. Many other researchers are performed to understand the correlation between Tr cells groups. More studies made a hope for treatment and therapy to prevent and modulate T-cell mediated disorders (Richard et.al., 2004). Regulatory T lymphocytes (CD4CD25) Tregs have a close relation in suppression of immunity(Hori et.al.,2004; Ramsdell ,2003 and Asseman and von Herrath,2002). Many other studies using experimental animals and human studies suggested that Treg cells may have a crucial role in the initiation of autoimmune disorders by decreasing or diminishing functions (Baecher-Allan et.al.,2004). Injection of Tergs into mice that susceptible to disease, prevents initiation of autoimmune disorders, while other strains of mice can develop gastritis, prostatitis and thyroiditis in the absence of C4CD25(Asano et. Al,1996; Sakaguchi et.al, 2001 and Takahashi 1998 ). Foxp3 is the abbreviation of  Forkhead  (FKH)  box protein 3belonging to a family of forkhead and have a crucial role in the production and function of  Tregs that is essential for tolerance of autoimmunity to self. The main task of immune system is to keep a balance between killing foreign bodies that attack human body and prevents self molecules from immune mediated damage as a sequence to inflammation and autoimmune disorders. Tregs have a role in controlling the above balance by suppression of immune response. The most important type of Tregs is that express CD4+ and Foxp3 which is largely studied because of therapeutic properties in immune disorders (Allan et. At.,2008). While Treg suppress activities of CD4+CD4+ T- lymphocytes, B- lymphocytes and Antigen presenting cell (APC) not well explained. Development and function of Foxp3 in Tregs were fully defined by many different researchers (Miyara and Sakaguchi,2007; Chen et.al.,2008 and Zuo et.al.,2007).