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Diagram of regulatory T cell, effector T cells and dendritic cell showing putative mechanisms of suppression by regulatory T cells. The molecular mechanism by which regulatory T cells exert their suppressor/regulatory activity has not been definitively characterized and is the subject of intense research.
The ways of Tr1 cells induction in vivo, ex vivo and in vitro differ and also envelop many different approaches but the molecular mechanism appears to be conserved. IL-27, together with TGF-β induces IL-10–producing regulatory T cells with Tr1-like properties cells.
Regulatory T cells are yet another distinct population of T cells that provide the critical mechanism of tolerance, whereby immune cells are able to distinguish invading cells from "self". This prevents immune cells from inappropriately reacting against one's own cells, known as an " autoimmune " response.
Regulatory T cells (T REG) need CD28 signal for their generation and ICOS signal for their peripheral maintenance and survival. In contrast, HVEM, GITR and CD30 are suppressing their activity. [2] [4] [6] Effector T cells are mainly regulated by TNFRSF molecules, such as 41-BB, CD27, OX40, DR3 or GITR, which enhance their proliferation and ...
The differentiated regulatory T cells subsequently migrate to the lamina propria, where they multiply. CX3CR1+ macrophages present in this environment secrete IL-10, which is required for the expansion of the regulatory T cell population. [35] In the lamina propria the regulatory T cell population creates a tolerogenic environment to food antigens.
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]
The clinical symptoms are caused by abnormalities of the immune system. Most patients develop reduced levels of at least one immunoglobulin isotype, and have low CTLA-4 protein expression in T regulatory cells, hyperactivation of effector T cells, low switched memory B cells, and progressive loss of circulating B cells. [26] [27] [31]
Depletion of regulatory T cells increases immune activation. Glut1 regulation is associated with the activation of CD4+ T cells, thus its expression can be used to track the loss of CD4+ T cells during HIV. [19] Antiretroviral therapy, the most common treatment for patients with HIV, has been shown to restore CD4+ T cell counts. [20]
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