1. T cell ontology Penny Morel 5/13/08

2. General issues Introduce “thymocyte” to replace immature Make definitions more precise. DN1 thymocyte - CD4 - CD8 - CD44 + CD25 - Introduce the concept of naïve versus antigen experienced T cell - instead of “mature” Add additional T helper subsets - introduce transcription factors as part of the definition

3. T cell development Pre T cell (ETP) Thymocyte immature T cell located in the thymus DN1 thymocyte CD4 - CD8 - CD44 + CD25 - DN2 thymocyte CD4 - CD8 - CD44 + CD25 + DN3 thymocyte CD4 - CD8 - CD44 lo CD25 + pre TCR +  T cell DN4 thymocyte CD4 - CD8 - CD44 - CD25 - pre TCR + DP thymocyte CD4 + CD8 + TCR lo undergoing positive selection DP thymocyte CD4 + CD8 + TCR hi undergoing negative selection SP thymocyte CD4 + CD8 - TCR hi SP thymocyte CD4 - CD8 + TCR hi NKT cell TCR + NK1.1 (CD56) + CD1 restricted Natural Treg CD4 + CD8 - TCR hi CD25 + FoxP3 +

4. Peripheral T cells Naïve T cell CD4 + CCR7 + CD62L + not exposed to antigen; blood and lymphoid organs CD8 + CCR7 + CD62L + IL-7R + not exposed to antigen; blood and lymphoid organs CD4 + CD25 + FoxP3 + CD62L + not exposed to antigen; blood and lymphoid organs (nTreg) Effector T cell CD4 + CCR7 - CD62L - antigen experienced; blood & peripheral tissues (helper) CD8 + CCR7 - CD62L - IL-7R - antigen experienced; blood & peripheral tissues (cytotoxic perforin and granzyme positive) Memory T cell Effector Memory T cell CD4 + CCR7 - CD62L - IL-7R + Ag experienced; blood & periphery CD8 + CCR7 - CD62L - IL-7R + Ag experienced; blood & periphery Central Memory T cell CD4 + CCR7 + CD62L + IL-7R + Ag experienced; blood & lymphoid organs CD8 + CCR7 + CD62+ - IL-7R + Ag experienced; blood & lymphoid organs

5. Types of Effector T cells (helper) T helper 1 (Th1): CD4 + T-bet + produce IFN-  ; cellular immunity to intracellular pathogens; DTH T helper 2 (Th2): CD4 + GATA-3 + produce IL-4; humoral immunity; immunity to extracellular parasites T helper 17 (Th17): CD4 + ROR  T produce IL-17; cellular immunity; immunity to extracellular bacteria T reg 1 (Tr1): CD4 + produce IL-10; (no signature TF) inhibit immune responses Induced Treg (iTreg): CD4 + CD25 + FoxP3 + produce TGF , IL-10; inhibit immune responses

6. Types of effector T cells (cytotoxic) Cytotoxic T cells (CTL): CD8 + perforin + granzyme B + ; kill infected targets Tc1: CD8 + T-bet + Eomes + produce IFN-  kill infected targets Tc2: CD8 + GATA-3 + produce IL-4. IL-13; less cytotoxic Tc17: CD8 + ?ROR  T + produce IL-17; ?cytotoxic Treg: CD8 + FoxP3 + suppress immune responses