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The four major subsets
of CD4 T cells
Tolerance
Immunity
STAT1/4
Th1
IL-2
IFN-γ
(TNF-α)
T-bet
STAT5
STAT5/6
nTreg
Th2
Foxp3
GATA3
IL-4
IL-5
IL-13
(IL-2)
(IL-6)
(IL-10)
(IL-9)
(IL-25)
(TNF-α)
Defense against
extracellular
parasites
Allergy
(IL-21)
(IL-26)
Defense against
extracellular
pathogens (fungi,
bacteria)
Autoimmunity
STAT3
Th17
RORγt
„Master Regulators“
IL-17
IL-22
Defense against
intracellular viruses
and bacteria
Autoimmunity
Angelika Schmidt
The growing family of
CD4 T cell subsets
Tolerance
Tfr
Immunity
Th1
Th3
nTreg
Th9
Th2
Tfh
Th22
Tr1
Th17
Tr35
Angelika Schmidt
T cells are activated by T cell
receptor (TCR) signaling
A simplified view of TCR signaling cascades
Adapted from Schmidt et al.,
Frontiers in Immunology, 2012
Angelika Schmidt
Regulatory T cells (Tregs)
suppress other immune cells
+
–
Prevention of autoimmunity, allergies, excessive immune reactions
Prevention of anti-tumor immunity
Angelika Schmidt
Tregs suppress T cell activation
by different mechanisms
IL-2
Cytokine
consumption
and cell death
induction
TGF-β
CD25
Inhibitory
cytokines
IL-10
Treg
granzymes
perforin
Indirect suppression
through DC inhibition
IL-35
CTLA-4
CD4+CD25++
Foxp3+
ATP, ADP
CD39, CD73
Suppressive
metabolites
adenosine
CTLA-4
CD80/
CD86
cAMP
DC
ICER
Transcriptional
repressors
Adapted from Schmidt et al.,
Frontiers in Immunology, 2012
Ikaros
Ca2+
NFAT
NF-ĸB
Suppression of TCR
signaling pathways
Tcon
CD4+CD25–
Foxp3–
Angelika Schmidt