HTHSCI 1DT3 Lecture Notes - Lecture 17: Barrier Function, Immunosuppression, Innate Immune System
23 Jun 2018
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T cell roles
Th17 in graft rejection
- Th17 cells have a role in AI; induction isn’t completely clear but TGF-beta and IL-6 seem
important
- Effector cytokines are IL-17, IL-21, IL-22
Thelper cells
- Weak cytotoxic activity, mainly secrete cytokines and activate other cells: CTLs, B, NK and
delayed type hypersensitivity
Tregs
= induce tolerance
- proven as thymectomy causes AI in murine models
- tolerance can be transferred with regulatory T cells into recipients, causing graft acceptance
- can be induced or naturally-occuring
- induced = CD8+ CD23-, Tr1, Th3, anergic T cells
- naturally-occuring = CD4+ CD25-, CD4+ CD25-, NK-T
- CD4+ CD25+ compose 5-10% of a healthy T cell population; generated in the thymus, expressing
FOXP3, CD4, CD25, CTLA-4, GITR; development and maintenance requires CD28-B7
costimulation and IL-2
Dendritic cells
- There are both immature and mature DC; immature ones have low co-stimulaotry molecules
expression, and can induce anergy in T cells
- “parking experiments” showed slow or no rejection of kidney which had previously been in
another recipient that was immunosupressed, as DCs had been inactivated by the immune
suppression and carried to the new kidney
- For T cells to be rendered anergic; the DCs need to NOT EXPRESS CD80/86 molecules
Enzymatic control of immune response to graft
IDO = catabolises tryptophan, forming a vital role preventing rejection of the foetus during pregnancy
by: removing source of essential amino acid and the action of kynurenines (which tryptophan is
converted to)
- DC expression of IDO is upregulated by the binding of CTLA-4, either on T cells or as CTLA4-Ig
- Can also be induced by viral infection / transduction
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