Tolerance - T-cell tolerance - Pheriperal

10 important questions on Tolerance - T-cell tolerance - Pheriperal

How can you recognize the Tregs?

Tregs express a high amount of FOXP3 transcription factor, but other T-cell subtypes do not express these.

What is regulatory tolerance?

This is a type of tolerance with the use of Treg cells. These cells can suppress self-reactive lymphocytes that recognize antigens different from those recognized by the Treg cells.

How to Tregs suppress self-reactive lymphocytes?

o Producing anti-inflammatory cytokines (IL-10 and TGF-b)
o Cytolysis: Kill activated T-cells
o Metabolic regulation: consume nutrients that other immune cells needed to be activated so that they can’t be activated. (IL-2 consumption)
o Modulate the DC maturation and function: prevent activation of other cells and promote tolerance.
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What is the difference between nTregs and iTregs?

Natural Tregs are formed in the thymus (80%) and play a role in the peripheral immune tolerance while iTregs are induced tregs that are induced in the periphery from naïve T-cells (20%) and play a role in the control of the inflammation reaction.

How are natural Tregs formed?

They are formed after selection in the thymus after binding to the MHC/auto-peptide.

How does Foxp3 block the production of IL-2?

The transcription factor Foxp3 expressed both on natural and induced Treg cells interferes with the interaction between AP-1 and NFAT at the IL-2 promotor, which then prevents the transcriptional activation of the gene and production of IL-2.

Why do Treg cells stop to production of IL2?

By the suppression of IL-2 the Tregs can regulate the immune response and maintain the immune homeostasis by limiting the proliferation of effector T cells.

What is the role of CD25 expression on Treg cells?

By expressing CD25, Treg cells steals IL-2 from naïve T cells which lack CD25 expression until activated. Therefore, they limit the availability if IL2 for T-cell activation.

How does CTLA-4 expression on Treg cells contribute to their inhibitory function?

They Bind the CD80/CD86 receptors on APC’s cells and competing with the B7 expression on the APC, and this prevents adequate co-stimulation of the naïve T-cells.

What is the function of IL10?

They are produced late in the immune response and inhibits the expression of MHC molecules and co-stimulatory molecules by APC’s.

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