Naive Th cells play a central role in modulating the immune response. They are activated by recognition of a peptide antigen bound to the class II major histocompatibility complex (MHC) on antigen-presenting cells (APCs) through the interaction with the T cell receptor. After activation, Th precursor (ThP) cells begin to divide and give rise to effector cells. These effector Th cells are CD4⁺ and can be divided into three main types with distinct cytokine secretions and functions: Th type 1 (Th1), Th type 2 (Th2), and most recently Th type 17 (Th17), expanding the group to what is now referred to as the Th1/Th2/Th17 paradigm.

TNFαIL-6

TNFαIL-6

TGFβIL-10IL-35

IL-15/IL-15R

Foxp3AHRSTAT5

IL-22TNFα

Dendriticcell

TGFβ

TGFβ + IL-6IL-21IL-23

IL-2IL-4IL-27IFNγT

Effector T

APC

RUNX1BATFIRF4

RORγtRORα4STAT3

AHR

CCR10CD4PDGFRTCR

ThPTh22

Treg

NKT

Th17

CD25CD4CD39CD73CD101FR4 (m)GARP (activated)

GITR/AITRTCRCXCR3CCR4CCR9CTLA-4

CD11CDEC205

TCRCD3

CD25CD49bCD69CD94CD160 (m)CD244NKG2DNK1.1Vα24Jα18TCR (h)Vα14Jα18TCR (m)

MHCIMHCII

IL-1R1IL-12RB1IL-13Rα1IL-21RIL-23RTCRCD4CD161CCR6

IL-4IFNγIL-17 (iNKT subset)

The T helper (Th) cell paradigm

SummaryFeature Th1 Th2 Th9 Th17 Th22 Treg Tfh

Surface expressionIL-12RB2IFNγRTim-3

IL-17RBTim-1 –

IL-1R1IL-12RB1IL-23RCCR6 (h)CD161 (h)IL-13Rα1

PDGFRCCR10

CD25CD39CD73CD101CD127lo

FR4 (m)GITR/AITR

CD84CXCR5IL-6RIL-21Rgp130

Unique cytokine expression IFNγIL-4IL-5IL-13

IL-9

IL-17AIL-17FIL-17AFIL-21IL-22

IL-22TNFα TGFβ IL-6

“Master regulator” transcription factor T-bet GATA3 – RORγt – Foxp3 BCL6STAT regulators STAT1, 4 STAT6 – STAT3 – STAT5 STAT3

Polarizing cytokinesIL-12IFNγIL-27

IL-4IL-25 (IL-17E)

IL-4TGFβ

IL-6TGFβIL-21

TNFαIL-6 TGFβ

IL-6IL-21CXCL13

Key

Differentiation

Negative regulation

Signal/ activation

Secretion

Transcriptional control

Cell-surface markers

(h) Human

(m) Mouse

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The T helper (Th) cell paradigm

TNFαIL-6

TNFαIL-6

TGFβIL-10IL-35

IL-15/IL-15R

IL-17AIL-17FIL-17AFIL-21IL-22IL-24IL-26

Foxp3AHRSTAT5

IL-22TNFα

Dendriticcell

TGFβ

TGFβ + IL-6IL-21IL-23

IL-2IL-4IL-27IFNγT

Effector T

APC

RUNX1BATFIRF4

RORγtRORα4STAT3

AHR

Stromalcell

IL-6IL-8

BCL6STAT3

CCR10CD4PDGFRTCR

ThPTh22

Treg

NKT

Th17

CD25CD4CD39CD73CD101FR4 (m)GARP (activated)

GITR/AITRTCRCXCR3CCR4CCR9CTLA-4

CD11CDEC205

TCRCD3

CD25CD49bCD69CD94CD160 (m)CD244NKG2DNK1.1Vα24Jα18TCR (h)Vα14Jα18TCR (m)

PodoplaninSTRO-1CD137

MHCIMHCII

IL-1R1IL-12RB1IL-13Rα1IL-21RIL-23RTCRCD4CD161CCR6

Antigen presentationCostimulatory signals

Dendriticcell

IL-6IL-21CXCL13

IL-27 (early)IL-12 p70 (+ IL-15) (m)TRANCE

TGFβIL-4

IL-2IL-4IL-15 (h)

IL-25IL-31IL-33

IL-8

Macrophage

TNFαTNFα

Perforin

Granzyme B

Perforin

Granzyme B

CTL

Granulysin

(natural killer)

IL-6IL-10

B cell

Plasma cell

IL-2IFNγTNFαTNFβ

IL-1IL-3IL-4IL-5IL-6IL-10IL-13GM-CSF

T-betRUNX3STAT1STAT4

GATA3STAT6

IL-9

IL-4

IFNγ

Tfh

Th1

Th2

Th9

CD15 (h)GR-1 (m)

PMN

CD11bCD14

DEC205CD11c

TCRCD8

CD94NKG2D

CD4TCR

TCRCD4CD30CCR8CXCR4Tim-1NOTCH1NOTCH2IL-17RB

ICOSTCRCD4IL-6RIL-21RCD84CD132CXCR5gp130

TCRTRANCETim-3FASLNOTCH3CD4CD26CD94CD195IL-12RB2IL-18RICOS

IL-10

BCRCD19

CD38 (m)CD27 (h)

NK cell

(lymphokineactivated killer)

LAK cell

(cytotoxic T)

(polymorphonuclear leukocyte)

IL-4IFNγIL-17 (iNKT subset)

For Research Use Only. Not for use in diagnostic procedures. © 2020 Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified. COL23856 0220

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