CD4 helper cells coordinate; CD8 cytotoxic cells kill
Mnemonic
“CD4 for 2, CD8 for 1”, the rule of eight:
- CD4 helper cells recognise antigen on MHC class II (4 x 2 = 8)
- CD8 cytotoxic cells recognise antigen on MHC class I (8 x 1 = 8)
MHC class II is on antigen presenting cells (dendritic cells, macrophages, B cells); MHC class I is on every nucleated cell, which is why cytotoxic cells can kill any infected or malignant cell.
The helper subsets:
- Th1 - drives cell mediated immunity and macrophage activation, through interferon gamma and interleukin 2. Against intracellular organisms
- Th2 - drives antibody and eosinophils, through interleukins 4, 5 and 13. Against parasites, and responsible for allergy
- Th17 - neutrophil recruitment at mucosal surfaces
- T regulatory - suppression and self tolerance, through interleukin 10 and TGF beta
HIV destroys CD4 cells, which is why the CD4 count measures immune damage and why the opportunistic infections are those normally controlled by cell mediated immunity.
Expansion
- CD4 helper: recognise antigen on MHC class II (on antigen presenting cells).
Coordinate the response by cytokine release
- Th1: interferon gamma, activating macrophages against intracellular organisms
- Th2: interleukin-4 and 5, driving antibody and eosinophil responses to parasites and in allergy
- Th17: neutrophil recruitment, defence against fungi and extracellular bacteria
- T follicular helper: B cell help and class switching
- CD8 cytotoxic: recognise antigen on MHC class I (on all nucleated cells). Kill virus-infected and tumour cells by perforin, granzymes and Fas
- Regulatory T cells (CD4, FoxP3): suppress responses and maintain self-tolerance
MHC class I presents endogenous (cytosolic) antigen; class II presents exogenous (phagocytosed) antigen. That difference explains why cytotoxic cells can survey every nucleated cell for viral infection.
HIV destroys CD4 cells, which is why it disables the whole adaptive response and predisposes to intracellular pathogens such as Pneumocystis, mycobacteria and cytomegalovirus.
Loss of regulatory T cell function causes autoimmunity, as in IPEX syndrome.