Stimulation of naive CD4+Foxp3− T cells in the presence of TGF-β results in the induction of Foxp3 expression and T suppressor function. However, Foxp3 expression in these induced regulatory T cells (iTreg) is unstable, raising the possibility that iTreg would not be useful for treatment of autoimmune diseases. However, When IL-2 is added, the Foxp3 expression is stabilized.
Why is this important, because the tumors secrete the TGF-β and the activated CD4+ T cells secrete the IL-2 for the propagation of the CD4+ T cells. This is the perfect storm for the tumor. The proliferation and survival the of the Tregs, makes it almost immposible to infiltrate the tumors’s microenviroment.
The Tregs compete for the screted IL-2. Depending on the location and how close the CD4+ T cell to the Tregs, The tregs can gain the upper hand by creating a IL-2 sink.
The Tregs must be neutralized to eliminate the surpressiveness that leads to tolarence of the immune system.
Neutralization of IL-2 or disruption of its signaling by deletion of Stat5 diminished the level of Foxp3 expression resulting in decreased suppressor function of the iTreg in vivo.
Blockade or depleting of the Tregs may be the only way to break the tolarence of the immune system.
“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~
Take Care,
Jimmy B
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