1. The four major subsets of CD4 T cells Angelika Schmidt Defense against intracellular viruses and bacteria Autoimmunity Th1 Defense against extracellular parasites Allergy Th2 Th17 Defense against extracellular pathogens (fungi, bacteria) Autoimmunity IL-2 IFN-γ IL-4 IL-5 IL-13 IL-17 IL-22 (TNF-α) (IL-21) (IL-26) Foxp3GATA3 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

2. The growing family of CD4 T cell subsets Angelika Schmidt Tolerance Immunity Th1 nTreg Th2 Th17 Tr35 Th3 Tr1 Tfr Th9 Th22 Tfh

3. T cells are activated by T cell receptor (TCR) signaling Angelika Schmidt Adapted from Schmidt et al., Frontiers in Immunology, 2012 A simplified view of TCR signaling cascades

4. Regulatory T cells (Tregs) suppress other immune cells Angelika Schmidt + Prevention of autoimmunity, allergies, excessive immune reactions – Prevention of anti-tumor immunity

5. Tregs suppress T cell activation by different mechanisms Angelika Schmidt Tcon Treg granzymes perforin IL-2 CD25 CD4 + CD25 – Foxp3 – CD4 + CD25 ++ Foxp3 + ICER Ikaros cAMP Ca 2+ NFAT NF-ĸB ATP, ADP adenosine CD39, CD73 CTLA-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 metabolites Indirect suppression through DC inhibition Transcriptional repressors Suppression of TCR signaling pathways