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