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Understanding Thymocyte Development and T Cell Subsets: Definitions and Classifications

This document introduces critical terminology in T cell biology, specifically replacing "immature" with "thymocyte" and refining definitions for various T cell stages. It details the different thymocyte subsets (DN1 to SP), their surface markers, and the distinction between naïve and antigen-experienced T cells. Additional classifications for T helper subsets are provided, highlighting the role of transcription factors in T cell development. This comprehensive analysis aids in better understanding T cell functions and the immune response.

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Understanding Thymocyte Development and T Cell Subsets: Definitions and Classifications

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  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- 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+

  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 cellCD4+ CCR7- CD62L- IL-7R+ Ag experienced; blood & periphery CD8+ CCR7- CD62L- IL-7R+ Ag experienced; blood & periphery Central Memory T cellCD4+ 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

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