CD28 signaling is a critical pathway required for effector T cell
expansion and for regulatory T cells inactivation, and FR104 exerts its immunomodulatory function by blocking CD28 signaling and thereby preventing effector T cells
but not regulatory T cells function, thereby promoting immune tolerance.
Treg cells release cytokines such as IL-10 and TGF-[beta], that suppress the activity of effector T cells as well as of APCs.
Second, when immune homeostasis is perturbed and inflammation erupts in the tissues, both natural Tregs and cytokine-induced adaptive Tregs traffic to the site of inflammation and curtail the functions of fully differentiated pathogenic effector T cells in the target tissue.
T regulatory cells, characterised by the expression of the cell surface marker CD25 and the transcription factor FoxP3, play a key role in maintaining this balance by suppression of the activity of effector T cells principally through cell-cell contact.
In vitro studies and in vivo adoptive transfer experiments revealed that CD4+CD25+ T cells from GM-CSFtreated mice could suppress effector T cell response and T1D.
Specificity of the histamine receptor on effector T cells
Regulatory T cells, which carry the Lag-3 protein on their surfaces, interfere with the action of effector T cells -- the "warrior" cells that orchestrate attacks on specific targets in the body, such as cancer cells and microorganisms.
The researchers showed that the ability of regulatory T cells to control an attack by effector T cells is substantially prevented or eliminated in the absence of Lag-3.
The braking action of regulatory T cells prevents the destructive effects of autoimmune diseases, such as diabetes type 1, which occurs when effector T cells mount an attack on the cells of the pancreas that produce insulin," Vignali said.
In mouse studies, the researchers first showed that regulatory T cells can protect against a potentially lethal, large-scale immune system attack by effector T cells that ordinarily would have caused a fatal lung disease.
Senior Director of Research at Unither Pharmaceuticals presented the abstract on April 18th as part of the conference proceedings covering "Regulatory and Effector T Cells
in Tumor Immunity".
These immunologic results from Trial STIR 2102 demonstrate a decrease in immune activation and an increase in memory effector T cells
in REMUNE(R) immunized subjects and support the results previously reported that therapeutic immunization may, through restoration of the patients immune system, have a positive impact on delaying virologic failure".