T cell ontology
Penny Morel
5/13/08
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
T cell developmentPre 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- CD44lo CD25+ pre TCR+
T cell DN4 thymocyte CD4- CD8- CD44- CD25- pre TCR+
DP thymocyte CD4+ CD8+ TCRlo undergoing positive selection
DP thymocyte CD4+ CD8+ TCRhi undergoing negative selection
SP thymocyte CD4+ CD8- TCRhi
SP thymocyte CD4- CD8+ TCRhi
NKT cell TCR+ NK1.1 (CD56)+ CD1 restricted
Natural Treg CD4+ CD8- TCRhi CD25+ FoxP3+
Peripheral T cellsNaïve 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 organsCD4+ 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
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+ RORT 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
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+ ?RORT+ produce IL-17; ?cytotoxic
Treg: CD8+ FoxP3+ suppress immune responses
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