T cell differentiation and function Flashcards
STATs for TH1 differentiation
STAT1 and STAT4
Cytokines for TH1 differentiation
IFNg (Stat1) and IL-12 (Stat4)
Induction of TH1 program
STAT1 and Stat4 can both induce Tbet
Tbet (hlx, Runx3, Ets) drive expression of IFNg and repress IL4
-Tbet represses function of Gata and RORc
-ITK - pTbet and which supresses gata3
STATs for TH2 differentiation
STAT5 or STAT6 can induce gata3
Stat3 also contributes to TH2 differentiation
Alternative induction of gata3
Notch can induce gata3 independent of stat6
Cmaf
Cmaf is a TF
expression driven by gata3
-drives expression of IL4
-not required for other TH2 cytokines
Cytokines for TH17
IL6 and IL23
STAT for TH17
STAT3 (induced by both IL6 and IL23)
Transcription factors for IL17 expression
Aryl Hydrocarbon receptor, Batf, IkBz, IRF4, Runx1, all promote IL17 expression
Inhibitors of TH17 program
Foxp3, GF1, Ets1
TCF-1 directly binds IL17 gene, also represses IL7r, thus constraining the survival
Induction of the treg program
IL-2 signals through stat5
Foxp3 maintenance of Treg program
- interferes with rorc (and TH17 development)
- directly regulates genes important for the treg program
Runx1 and Treg program
Runx1 can either interact with rorc to promote Th17 or with Foxp3 to promote Treg
-Runx proteins can also regulate expression of rorc and foxp3
Foxo and Treg program
Foxo1 and foxo3 promote tregs
Tregs and lineage supression
Tregs supress other effector responses using components of the transcriptional machinery that are important for the target effector response
Sat1b
Chromatin organizer that is repressed by foxp4 so that it can’t remodel chromatin at cytokines that drive other effector lineages
Surface phenotype associated with enhanced CD8 memory generation
CD127hi CD27+ KLRG1lo
Also express BCL2
Requirements for CD8 memory maintenance
Antigen independent
IL-7 and IL-15 dependent
Tcm
Central memory T cells - greater proliferative potential upon reactivation but lower expression of effector cytokines. Express high levels of IL-2 and have high migratory capacity
Tem
effector memory T cells that constitutively express cytotoxic proteins. Decreased proliferative potential and IL-2 production. High migratory capacity and effector function/cytotoxicity
these will be enriched upon repetitive vaccinations or successive infections.
Tcm Surface phenotype
CD62Lhi CCR7 hi
Tem surface phenotype
CD62L low CCR7 low
Trm
Tissue resident memory cells that do not recirculate
Decreased proliferation, IL-2 production and migration
increased effector functions and cytotoxicity
Trm surface phenotype
CD103hi CD69hi CD62Llow CD27low
Tissue specific homing receptors
Tcm location
LN, spleen blood
Tem location
Spleen, blood, liver
Trm
Skin, gut, brain
main proinflammitory cytokines during viral/other intracellular infections
Type I IFN, IFNg, IL-2, IL-12, IL-27, IL-33
TH1 SOCS member
SOCS5
TH3 SOCS member
SOCS3
TH17 SOCS member
SOCS1