CCR10 CD4 PDGFR TNFα Th22 TCR TNFα I L- 6 I L- 6 ThP

TGFβ I L-2 2 CD11C TNFα DEC205

Dendritic cell TGFβ + IL-6 I L-21 I L-23

Treg Foxp3 AHR STAT5 I L-2 CD25 I L- 4 CD25 GITR/AITR CD49b IL-27

CD4 TCR CD69 IFNγ T I L-1R1 CD39 CXCR3 CD94 I L-12R B1 CD73 CCR4 CD160 (m) I L-13 R α1 CD101 CCR9 TGFβ CD244 I L-21R FR4 (m) CTLA-4 I L-10 NKT NKG2D I L-23 R GARP (activated) IL-35 NK1.1 TCR Vα24Jα18TCR (h) CD4 Vα14Jα18TCR (m) CD161 CCR6

Effector T I L- 4 IFNγ I L-17 ( i N K T subset) Th17 MHCI APC TCR MHCII CD3 RUNX1 BATF IRF4 RORγt I L-15 / I L-15 R RORα4 STAT3 AHR The T helper (Th) cell paradigm

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. The T helper (Th) cell paradigm DEC205 Dendritic CD11c cell CCR10 CD4 CD4 PDGFR TCR TNFα Th22 TCR TNFα Antigen presentation I L- 6 I L- 6 ThP Costimulatory signals TGFβ Th9 I L- 4

TGFβ I L-2 2 CD11C I L- 9 TNFα I L-2 I L-25 DEC205 I L- 4 IL-31 I L-15 ( h) IL-33 TCR CD4 Dendritic CD30 cell TGFβ + IL-6 I L-21 CCR8 I L-23 I L- 6 CXCR4 Treg I L-21 IL-27 (early) Th2 Tim-1 Foxp3 CXCL13 IL-12 p70 (+ IL-15) (m) NOTCH1 AHR TRANCE NOTCH2 STAT5 I L-2 I L-17R B CD25 I L- 4 IFNγ

CD25 GITR/AITR CD49b IL-27 T I L-10 CD4 TCR T-bet GATA3 CD69 IFNγ I L-1R1 CD39 CXCR3 RUNX3 STAT6 CD94 I L-12R B1 CD73 CCR4 STAT1 CD160 (m) I L-13 R α1 I L- 4 CD101 CCR9 STAT4 TGFβ CD244 I L-21R FR4 (m) CTLA-4 I L-1 I L-10 NKG2D I L-23 R GARP (activated) NKT Th1 IL-3 IL-35 NK1.1 TCR TCR Vα24Jα18TCR (h) TRANCE I L- 4 CD4 I L- 5 Vα14Jα18TCR (m) CD161 Tim-3 FASL I L- 6 CCR6 ICOS Key NOTCH3 I L-10 TCR Effector T CD4 I L-13 Differentiation I L- 4 CD4 CD26 GM-CSF Negative IFNγ I L- 6 R I L-2 CD94 regulation I L-17 ( i N K T Tfh I L-21R IFNγ CD195 Signal/ subset) CD84 activation Th17 TNFα I L-12R B 2 CD132 Plasma cell Secretion MHCI APC TNFβ I L-18 R TCR CXCR5 MHCII ICOS Transcriptional CD3 RUNX1 gp130 B cell control BATF Cell-surface BCL6 markers IRF4 STAT3 CD38 (m) RORγt (h) Human CD94 CD27 (h) I L-15 / I L-15 R RORα4 NKG2D BCR I L- 6 NK cell (m) Mouse STAT3 CD19 I L-17A I L-10 AHR (natural killer) I L-17F Summary Feature Th1 Th2 Th9 Th17 Th22 Treg Tfh I L-17A F CD25 CD11b I L-1R1 I L-21 Granulysin TCR CD39 CD84 I L-12R B1 CD14 I L-12R B2 CD73 CXCR5 I L-2 2 CD8 I L-17R B I L-23 R PDGFR Macrophage Surface expression IFNγR – CD101 I L- 6 R Tim-1 CCR6 (h) CCR10 I L-24 Tim-3 CD127lo I L-21R Perforin CTL CD161 (h) I L-26 FR4 (m) gp130 (cytotoxic T) I L-13 R α1 GITR/AITR Granzyme B I L-17A Granzyme B I L- 4 I L-17F TNFα I L-22 I L- 8 Unique cytokine expression IFNγ I L- 5 I L- 9 I L-17A F TGFβ I L- 6 TNFα TNFα I L-13 I L-21 I L-22 I L- 6 Stromal “Master regulator” transcription factor T-bet GATA3 – RORγt – Foxp3 BCL6 I L- 8 cell Perforin STAT regulators STAT1, 4 STAT6 – STAT3 – STAT5 STAT3 LAK cell I L-12 I L- 6 I L- 6 (lymphokine I L- 4 I L- 4 TNFα PMN Polarizing cytokines IFNγ TGFβ TGFβ I L-21 activated killer) I L-25 ( I L-17E ) TGFβ I L- 6 Podoplanin (polymorphonuclear IL-27 I L-21 CXCL13 STRO-1 leukocyte) CD15 (h) CD137 GR-1 (m) Find out more at thermofisher.com/immunoassay Find out more at thermofisher.com/immunoassay

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