9. Foxp3 and Regulatory T Cells

Question 1

Tregs are marked by [high/low] CD25 expression

Answer 1

Tregs are marked by high CD25 expression

Question 2

Tregs limit TCR induced proliferation of conventional CD4 and CD8 T cells in culture
TRUE OR FALSE

Answer 2

TRUE

Question 3

Tregs are a regulatory subset of [CD4+/CD8+] T cells

Answer 3

Tregs are a regulatory subset of CD4+ T cells

Question 4

Tregs express the canonical transcription factor Foxp3

TRUE OR FALSE

Answer 4

TRUE

Tregs also express several other less definitive surface markers e.g. CD25

Question 5

Treg differentiation:

Answer 5

“Natural”: nTregs - Differentiate in the thymus in response to strong peptide-MHCII signals (i.e. they are self antigen specific)

“Induced”: iTregs - Induced from naive T cells in the periphery in response to peptide-MHCII signals in the presence of TGFbeta

Question 6

Tregs control inflammation and all known types of the immune response via:

Answer 6

1. Production of immunomodulatory cytokines (e.g. IL-10, TGFbeta) that can suppress the pro-inflammatory responses of T cells, NK cells, B cells, DCs, and macrophages.
2. Enzymatic activity of the ectoenzymes CD39 and CD73. Highly expressed on Treg cell surface, enables conversion o extracellular ATP to AMP, AMP acts through adenosine receptors on immune cells to suppress inflammatory responses.
3. High expression of CD25 (the high-affinity alpha-subunit of the IL-2 receptor) leads to IL-2 depletion/consumption. This restrains the responses of CD8 T cells.
4. High expression of CTLA-4 enables down-regulation of co-stimulatory molecules CD80 and CD86 expression on DCs

Question 7

Tregs play a major role in immune homeostasis:

Answer 7

Mutations in Foxp3 gene -> Autoimmune disorder “IPEX”, a rare genetic disorder of immune dysregulation

Question 8

The transcription factor BLANK is critical for the development and function of Tregs

Answer 8

The transcription factor Foxp3 is critical for the development and function of Tregs

Question 9

Foxp3 functions as a key transcriptional regulator in Treg cells
TRUE OR FALSE

Answer 9

TRUE

Question 10

Foxp3 can modulate the accessibility of genes to several transcription factors through its interaction with chromatin remodellers, including the HATs P300 and TIP60.
TRUE OR FALSE

Answer 10

TRUE

Question 11

Foxp3 interacts with multiple transcription factors known to be involved in activation, differentiation, and response of CD4+ T cells to TCR stimulation
TRUE OR FALSE

Answer 11

TRUE