Lecture 16 - CD4 T cell subsets (2 of 2) Th17 + regulatory T cells

Question 1

What kind of pathogens do Th1 cells clear?

Answer 1

intracellular bacteria and protozoa

Question 2

What kind of pathogens do Th2 cells clear?

Answer 2

parasitic worms

Question 3

What is the role of Th17 cells?

Answer 3

to initiate effector immune responses against pathogens that cannot be cleared by Th1 or Th2 cells
-extracellular bacteria and fungi

Question 4

How are Th17 cells induced?

Answer 4

1. PAMPs bind DC PRR; Antigen uptake; MHC-II presentation
2. DC produces SIGNAL 3 = Active TGFβ + IL-6
3. Initial Th17 differentiation
4. IL-23 promotes survival + expansion of Th17 cells

Question 5

What are the effector functions of Th17 cells?

Answer 5

recruited to sites of inflammation

recruit neutrophils to sites of inflammation

Question 6

Summarise Th17 cell role

Answer 6

DC produce active TGFβ, IL-6, IL-23 in response to fungi or extracellular bacteria = Signal 3 for Th17 differentiation
TGFβ + IL-6 induce initial Th17 differentiation
IL-23 promotes expansion + survival of Th17 cells
Lineage-specific TF for Th17 cells is RORγT
Th17 cells produce IL-17
This induces non-immune cells at sites of infection to produce CXCL8 = neutrophil chemoattractant
…and recruited neutrophils kill pathogen

Question 7

What is the effector mechanism of Th1 cells?

Answer 7

macrophage activation

Question 8

What is the effector mechanism of Th2 cells?

Answer 8

IgE arming of granulocytes

Question 9

What are the two types of regulatory T cell?

Answer 9

natural - differentiate in thymus

induced - differentiate in periphery

Question 10

What causes natural Tregs to differentiate in the thymus?

Answer 10

nTregs develop in thymus in response to “stronger than normal” TCR stimulation
i.e. bind to self peptide MHC-II more strongly than normal T cell…
… BUT not strong enough to delete
Stronger TCR stimulation induces expression of Treg lineage-specific transcriptional factor = Foxp3
Hypothesised nTreg are self-reactive

i.e. function to inhibit strongly auto-reactive T cells that would cause autoimmunity

Question 11

What causes “induced Tregs” to differentiate in periphery?

Answer 11

Signal 3 for iTreg generation is TGFβ (in absence any inflammatory signal)
iTreg potentially specific for any antigen…
…pathogens, self-antigens, commensal organisms

Question 12

How do Tregs suppress immune responses?

Answer 12

nTreg + iTreg suppress immune responses by similar mechanisms

A. Cell surface molecules:
1. Regulatory T cells express high levels of CTLA-4
CTLA-4 binds + sequesters DC CD80 & CD86
Stops DCs providing signal 2 to naive T cells i.e. CD28 costimulation
CTLA-4 can physically rip CD80 & CD86 from APCs
2. Regulatory T cells express high levels of IL-2 receptor
TCR stimulation causes activated CD4 T cells to produce IL-2 = proliferation
Tregs outcompete activated T cells for IL-2 i.e. stop proliferation

B. Secretion of immunosuppressive cytokines
Inhibit IL-12 production by DCs (no Th1)
Reduce MHC-II & CD80/CD86 levels on DC
Inhibit T cell proliferation
Generate more Tregs (TGFβ)