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CD4+ T Cells and their role in immunity
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Lecture notes detailing CD4+ T cells and what roles they play in immunological processes
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Lecture 12 – CD4+ T Cells, Key Regulators ofImmunity
Life History of T Lymphocytes
- Precursors mature in the thymus.
- Naïve CD4+ and CD8+ T cells enter the circulation.
- Naïve T cells circulate throughout the lymph nodes and locate antigens.
- Activation of naïve T cells in the lymph node, development of effector cells.
- Activation of effector T cells at the site of infection, eradication of the microbe.
Naïve T Cell Signals Required
Signal 1
For CD4+ T cells –
- Interaction with MHC II/peptide complex.
- CD4 binds with MHC Class II.
- Signalling by CD3 on the T cell.
- Usually supplied by a professional APC.
For CD8+ T cells-
- Interaction with MHC I/peptide complex.
- CD8 binds to the MHC Class I.
- Signalling by CD3 on the T cell.
- Can be supplied by most nucleated cells.
Signal 2
Co-stimulation
- Lots of potential receptor/ligand interactions.
- APC dictates what the T cell should do.
- Determines T cell activation.
- Also qualitative:
o Tells the T cell what response to make.
o Make cytokines or not?
o What kind of cytokines?
o How much killing?
o How many divisions should I complete?
Antigen-Presenting Cells
Professional APCs constitutively express MHC class I and II.
Non-professional APCs (like keratinocytes) can upregulate MHC Class II in response to IFN-
gamma.
Professional APCs are very responsive to pattern recognition receptors or other
inflammatory signals.
PRRs/inflammation leads to the upregulation of co-stimulatory ligands.
, Dendritic cells are major APCs of the body:
- APCs are master regulators of the immune system Controls T cells T cells control B cells.
First Step in Adaptive Immunity: Dendritic Cell Maturation
- DC requires presence of antigen and evidence of danger/pathogen to be fully active.
- DC maturation and migration occurs at the same time.
Immature Dendritic Cells
Decrease co-stimulatory molecules.
Decreased MHC Class II expression.
Decreased secretion of pro-inflammatory cytokines.
Increased phagocytic capacity.
Decreased CCR7 expression.
Decreased glycolysis.
Pathogens, cytokines, PAMPs, DAMPs
Mature Dendritic Cells
Increase co-stimulatory molecules.
Increased MHC Class II expression.
Increased Secretion of pro-inflammatory cytokines.
Decreased phagocytic capacity.
Increased CCR7 expression.
Increased glycolysis.
B7-CD28: A Co-stimulatory Molecule
B7 is expressed on resting DCs but increased by activation.
Signals via CD28, tells the cell along with CD3:
- Divide.
- Do not die.
- Differentiate.
Other Co-stimulatory Interactions
- CD28/B7 is well studied and has many interactions.
- The key ones are 4-1BB/OX40/CD27.
- Not clear why there’s so many but may be:
o Activate with delayed kinetics.
o Qualitative differences.
o Different effects on different T cell subsets.
4-1BB preferentially activates CD8+ T cells, OX40 prefers CD4+ T cells.
Dendritic Cell Licensing
DC activates CD4+ T cell but it is a 2-way interaction.
Activated CD4+ T cell signals to DC via CD40.
Further activates the DC to provide additional signals to other cells.
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