“
“Regulatory T (Treg) cells represent one of the main mechanisms of regulating self-reactive immune cells. Treg cells are thought to play a role in down-regulating immune responses to self or allogeneic antigens in the periphery. Although the function of Treg cells has been demonstrated in many experimental settings, the precise mechanisms and antigen specificity often remain unclear. In a hepatitis B e antigen–T-cell receptor (HBeAg-TCR)

double transgenic mouse model, we observed a phenotypically unique (TCR+ CD4−/CD8− CD25+/− GITRhigh PD-1high FoxP3−) HBeAg-specific population that demonstrates immune regulatory function. This HBeAg-specific double-negative regulatory cell population proliferates vigorously in vitro, in contrast to any other known regulatory population, Cisplatin concentration in an interleukin-2-independent manner. The primary function of the immune system

is to protect the self from pathogens. A highly effective and dynamic cellular network has evolved to signal the presence of pathogens and initiate a response that is specific for the invading pathogen while maintaining tolerance to self. Distinguishing between self and non-self is a fundamental property of the immune system and is accomplished by a variety of mechanisms. A function of regulatory T (Treg) cells EPZ-6438 clinical trial is to prevent self-reactive immune cells from damaging self. The Treg cells, particularly CD4+ CD25+ conventional Treg (cTreg) cells, are thought to play a role in down-regulating immune responses to self or allogeneic antigens in the periphery.1–4 Although the function of Treg cells has been shown in a number of in vivo models of autoimmunity and transplantation, the precise mechanism and antigen specificity often remains unclear.5 In 1971 it was first suggested that Treg cells had the ability to transfer antigen-specific tolerance to naive animals.6 Even though a role for regulatory cells during an immune response was widely accepted, the existence of Treg cells was controversial until a specific Celecoxib surface marker was described by Sakaguchi et al.7 Conventional Treg cells constitutively express a variety of cell

markers, such as CD4, CD25, CD45RBlow, CD62 ligand (CD62L), CD103, as well as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR).7–14 Although cTreg cells express CD4+ CD25+, CD25 is not a specific marker for cTreg cells. Other cell markers (i.e. CTLA-4, GITR and CD103) are also not exclusive markers for Treg cells, because in most cases they are up-regulated on effector T cells upon activation. The transcription factor Forkhead box P3 (FoxP3) is predominantly expressed on Treg cells and appears to be expressed at the thymic CD4+/CD8+ stage.15–18 In contrast to the cell surface markers mentioned above, FoxP3 is not observed in non-Treg cells upon activation or differentiation into T helper type 1/ type 2 cells, nor in natural killer T cells.