11. IELs

Question 1

Are IELs found WITHIN or OUTWITH the epithelial layers

Answer 1

IELs are found WITHIN the epithelial layer

IELs = Intraepithelial T Lymphocytes

Question 2

Do IELs meet APCs?

Answer 2

IELs don’t meet APCs due to their presence within the epithelial layer.

Question 3

IELs contain both BLANK and BLANK T cell subsets

Answer 3

IELs contain both conventional and unconventional T cell subsets

Question 4

Different types of IELs are differentially distributed along the gut
TRUE OR FALSE

Answer 4

TRUE

This means they must have different functions, but that is currently unknown.

Question 5

Development of IELs:

Answer 5

Conventional:

• Thymus
• DP cell -> CD4+ or CD8+ naive cell -> Circulate through blood and lymph -> Enter GALT - > Recognise antigen in GALT -> Causes up-regulation of alpha4beta7 (integrin) and CCR9 (chemokine receptor)

Unconventional (alpha/beta):

• “Agonist Selection” (Strong TCR signals)
• DN effector cell, alpha4beta7 integrin targets these cells to the gut

Unconventional (gamma/delta):

• DN TCRVgamma7+ cell in thymus
• Normal T cell development, exit thymus as DN naive cell expressing alpha4beta7 and CCR9
• Circulate through blood and lymph -> Enter GALT where they recognise a ligand for Vgamma7+ receptor -> Proliferation of cells

For all 3 types, the final maturation occurs in the gut and involves TGFbeta, alphaEbeta7 integrin, and IL-15

Question 6

Low levels of IL-15 =
No IL-15 =
Stressed Epithelial Cells up-regulate IL-15 =

Answer 6

IELs maintained
IELs don’t survive
IELs proliferate and increase cytotoxic effector function -> Cells with up-regulated IL-15 are targeted for cell death -> IL-15 returns to normal levels (Process corrupted in Coeliac disease, IL-15 levels don’t return to normal)

Question 7

Functions of IELs:

Answer 7

Tissue Immune Surveillance:

• IELs express Granzyme A and B - cytotoxic proteases
• IELs express activatory and inhibitory NK receptors
• IELs express cytokines (such as IFNgamma and TNF) that cause apoptosis in epithelial cells
• Produce chemokines (such as CCL5) to recruit other immune cells

Maintenance of Barrier Function:

• IELs constitutively express antimicrobial peptides
• Express keratinocyte growth factor and amphiregulin, which support epithelial growth
• Aid in proper mucus production and mucin glycosylation