T-Cell Development

Question 1

In the thymus, HSCs develop and mature into…

Answer 1

• CD4 (helper T)
• CD8 (cytotoxic T)
• natural killer T
• Treg

Question 2

In embryological development, when does the thymus begin to produce T-cells?

Answer 2

at the 12th-13th week in utero (mature T-cells egress the thymus at the 13th-14th week)

Question 3

When is the peripheral T-cell pool established?

Answer 3

The T-cell pool and its repertoire is established before birth

Question 4

All TEC are derived from _________. Expression of ______ is essential for functional maturation of TEC.

Answer 4

endoderm; FOXN1

Question 5

Which cytokines do thymic epithelial cells produce?

Answer 5

IL1, IL6, IL7, IL15, SCF, TSLP

Question 6

What are the cell surface ligands of thymic epithelial cells?

Answer 6

delta-like 1 and delta-like 4 (ligands for Notch receptor)

Question 7

What is the process by which the thymus deletes autoreactive T-cells?

Answer 7

negative selection (happens only in the thymus)

Question 8

Where in the thymus are macrophages and dendritic cells concentrated?

Answer 8

cortico-medullary junction

Question 9

What are the 4 distinct stages of development in the generation of mature T-cells?

Answer 9

1) T lineage commitment: restriction of lineage choices
2) Proliferation: expansion of committed cells
3) Differentiation: gaining new surface markers
4) Maturation: selection and gaining of immune functions

Question 10

Pre-T cells express ________ for _________.

Answer 10

RAG1 and RAG2; rearrangement of TCR γ, δ, β.

Question 11

In which disease is the IL7Rγ chain implicated?

Answer 11

SCID-X1

Question 12

Which TCR chains form the pre-TCR?

Answer 12

combo of rearranged TCRβ gene with pTα (surrogate α chain) forms pre-TCR; signaling through this receptor induces a significant proliferation of ISP cells

Question 13

What is β selection?

Answer 13

selection for functionally rearranged TCRβ, which terminates rearrangement by degrading RAG proteins, and induces rapid/vigorous proliferation

Question 14

Do TCRVα chains undergo allelic exclusion?

Answer 14

No - it is possible that there are 2 different rearranged Vα chains, each associated with a common Vβ

Question 15

How does a T-cell reach the double positive stage?

Answer 15

After β selection ISP cells express CD8+ and develop into CD4+CD8+ double positive cells. RAG is re-expressed, and rearrangement of TCRVα genes is initiated.

Question 16

A syndrome in which there is a defect in MHC II expression, causing the development of CD4+ T-cells to be affected.

Answer 16

Bare Lymphocyte Syndrome (BLS)

Question 17

What is the significance of positive selection?

Answer 17

It ensures that each T-cell only has a single functional specificity and therefore coordinates the maturation of of CD4+ and CD8+ T-cells.

Question 18

What is the basis for intrathymic negative selection?

Answer 18

A TCR on a DP cell binds antigen/MHC with high affinity and is then signaled to undergo apoptosis. (BM-derived macrophages and DCs in the corticomedullary junction are the prominent cell types that induce neg. selection)

Question 19

_________ have been shown to express organ-specific antigens that mirror peripheral tissue antigens.

Answer 19

mTEC (medullary thymic epithelial cells)

Question 20

Treg cells are developed in the thymus from ______ T-cells. (CD marker)

Answer 20

CD3+CD4+

Question 21

Increasing or decreasing levels of Treg have been found to be associated with cancer?

Answer 21

increasing

Question 22

Where are NKT cells primarily found?

Answer 22

liver, spleen, BM, and lymph nodes (not many found circulating)

Question 23

What is the CD marker for NKT cells?

Answer 23

CD4+ or CD4-CD8-

Question 24

What are the main functions of NKT cells?

Answer 24

• immunoregulation (TH1 cytokines and Th2 cytokines)

- cytotoxicity

Question 25

What is the function of TCRδ1 cells?

Answer 25

cytotoxic activity - kill stressed epithelial cells

Question 26

What is the function of TCRγ9δ2 cells?

Answer 26

• anti-microbial immunosurveillance
• recognize intracellular bacteria
• carry out immune regulation through production of cytokines like IFN-γ (affects cytotoxicty of NK and NKT cells)
• majority of circulatory TCRγδ cells

Question 27

What are CD1 proteins?

Answer 27

• transmembrane proteins distantly related to MHC molecules but lack polymorphism
• 4 proteins: CD1a, CD1b, CD1c, and CD1d (each encoded by diff. gene)

Question 28

What is the TCRγδ repertoire restricted to?

Answer 28

only 3Vδ and 7Vγ

Question 29

What is the significance of the AIRE transcription factor?

Answer 29

It is part of the mechanism that eliminates self-reactive T-cells that could cause autoimmune diseases.