the four major subsets of cd4 t cells angelika schmidt defense against intracellular viruses and...

The four major subsets of CD4 T cells

Angelika Schmidt

Defense against intracellular viruses and bacteriaAutoimmunity

Th1

Defense against extracellular parasitesAllergy

Th2

Th17

Defense against extracellular pathogens (fungi, bacteria)Autoimmunity

IL-2IFN-γ

IL-4IL-5IL-13

IL-17IL-22

(TNF-α)

(IL-21) (IL-26)

Foxp3 GATA3

T-bet

RORγt

STAT5

STAT1/4

STAT5/6

STAT3

(IL-2) (IL-6) (IL-10)(IL-9) (IL-25) (TNF-α)

„Master Regulators“

Tolerance Immunity

nTreg

The growing family of CD4 T cell subsets

Angelika Schmidt

Tolerance Immunity

Th1

nTreg Th2

Th17 Tr35

Th3

Tr1

Tfr

Th9

Th22

Tfh

T cells are activated by T cell receptor (TCR) signaling

Angelika SchmidtAdapted from Schmidt et al., Frontiers in Immunology, 2012

A simplified view of TCR signaling cascades

Regulatory T cells (Tregs) suppress other immune cells

Angelika Schmidt

+ Prevention of autoimmunity, allergies, excessive immune reactions

– Prevention of anti-tumor immunity

Tregs suppress T cell activation by different mechanisms

Angelika Schmidt

Tcon

Treggranzymesperforin

IL-2

CD25

CD4+CD25–

Foxp3–

CD4+CD25++

Foxp3+

ICERIkaros

cAMP

Ca2+

NFATNF-ĸB

ATP, ADP

adenosine

CD39, CD73CTLA-4

DC

CTLA-4

CD80/CD86

TGF-β

IL-10

IL-35

Adapted from Schmidt et al., Frontiers in Immunology, 2012

Cytokine consumption and cell death

induction

Inhibitory cytokines

Suppressive metabolitesIndirect suppression

through DC inhibition

Transcriptional repressors

Suppression of TCR signaling pathways