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T cells: the usual subsets Chen Dong and Gustavo J. Martinez

T cells have important roles in immune responses and function by directly secreting soluble mediators or important for adaptation of immune responses in different microenvironments and might be particularly through cell contact-dependent mechanisms. Many subsets have been characterized. Although relevant for host defence against pathogens that colonize different tissues. Distinct T cell subsets, or effector T cells were originally considered to be terminally differentiated, a growing body of evidence has differentiation states, can be identified based on the cell surface markers expressed and/or the effector challenged this view and suggested that the phenotype of effector T cells is not completely fixed but is molecules produced by a particular T cell population. This Poster summarizes our current understanding of more flexible or plastic. T cells can have ‘mixed’ phenotypes (that is, have characteristics usually the surface markers, transcriptional regulators, effector molecules and functions of the different T cell associated with more than one T cell subset) and can interconvert from one subset phenotype to another, subsets that participate in immune responses. Further knowledge of how these T cell subsets are regulated IMMUNOLOGY although instructive signalling can lead to long-term fixation of cytokine memory. T cell plasticity can be and cooperate with each other will provide us with better tools to treat immune-related diseases.

Cytotoxic T cell Exhausted T cell Anergic T cell TR1 cell Natural TReg cell NKT cell CD8αα T cell Surface αβ TCR, CD3, CD8 Surface CD3, CD8, PD1, Surface αβ TCR, CD3, BTLA Surface αβ TCR, CD3, CD4 Surface phenotype αβ TCR, CD3, CD4, CD25, CTLA4, GITR Surface phenotype NK1.1, SLAMF1, SLAMF6, TGFβR, Surface αβ or γδ TCR, CD3, phenotype phenotype TIM3, 1B11, LAG3 phenotype phenotype Transcription factors FOXP3, STAT5, FOXO1, FOXO3 Vα14, Jα18 (mouse) phenotype CD8αα, B220 Transcription EOMES, T-bet, BLIMP1 Transcription BLIMP1 Effector GRAIL, CBL-B, ITCH, NEDD4 Vα24, Jα18 (human) Effector IL-10, TGF Transcription Not known Effector molecules secreted IL-10, TGFβ, IL-35 β factors factors factors factors Transcription PLZF molecules Function Mediate immunosuppression and tolerogenic responses factors secreted Effector Perforin, granzyme, IFNγ Function Generated in response Function These cells are generated Effector IL-10 through contact-dependent and -independent molecules to chronic - following TCR activation in molecules mechanisms. These cells are generated in the . Effector molecules IL-4, IFNγ, IL-17A Function Intraepithelial secreted mediated TCR the absence of co-stimulatory secreted secreted are found in the gut. They can stimulation. These signals, which leads them develop intra- or extra- Function Cytotoxic; kill infected and Function Immunosuppression Function Can have both pro- and anti-inflammatory cells express inhibitory to become unresponsive to Inducible TReg cell thymically. They express or transformed cells and thereby mediated by IL-10 functions. Have been shown to modulate immune αβ receptors and lack subsequent stimulatory signals. Surface phenotype αβ TCR, CD3, CD4, CD25, CTLA4, GITR TCRs. TCR+ cells express protect the host from viral production. These cells responses in several different settings, including γδ γδ effector cytokine They are functionally inactive KGF, whereas TCR+ cells do infections and cancer. Direct are generated from naive Transcription factors FOXP3, FOXO1, FOXO3, STAT5, SMAD2, SMAD3, SMAD4 cancer, autoimmunity, allergy, infection and graft- αβ production; they cells and fail to proliferate or not. Most TCRs are killing is mediated by secretion of T cells in the presence of Effector molecules secreted IL-10, TGF versus-host disease. αβ therefore fail to mount produce IL-2. Their generation β enriched for self-reactivity. perforin and granzymes, which TGF and IL-27 or in the Other features SAP expression. CD1-restricted TCR. effective antiviral may be important for avoiding β Function Promote immunosuppression and tolerance by They require microglobulin- cause apoptosis of target cells. presence of the immuno­ MAIT cells express an invariant TCR -chain β2 immune responses. autoimmune responses. contact-dependent and -independent mechanisms. α dependent MHC class I Other In humans, mainly CD45RO+. Some suppressive drugs (V 33J 19 in mice; V 7.2J 19 in humans). These cells are generated from naive T cells in the α α α α expression for their generation features terminally differentiated CTLs in Other Increased expression of p27KIP1, vitamin D3 and MAIT cells are MR1 restricted (not CD1 restricted) periphery and, at least in some cases, TGFβ and IL-2 and/or homeostasis. They can humans re-express CD45RA. features which leads to cell cycle arrest. dexamethasone. but have similarities to NKT cells. are important for their differentiation. have regulatory functions through the production of IL-10 and TGFβ. CD4 10’0µm TCR CD8 CD4 TCR TCR SLAMF1 TCR γδ TCR CD3 Cytokine CTLA4 SLAMF6 CD8αα TCR CD3 Chemokine GITR CD3 TCR NK1.1 TGFβR TCR CD8 PD1 TIM3 1B11 CD3 8’0µm BTLA receptor CD25 IL-7R B220 TCR CD62L LAG3 CD44 CD3 CD3 CD3 CD3 IL-7R CD3 CCR7 6’0µm CCR7

4’0µm Naive Cytotoxic Exhausted Anergic Helper Regulatory Memory NKT γδ CD8αα

+ CD4 αβ T cell TH1 cell TH17 cell Central γδ T cell Surface phenotype αβ TCR, CD3, CD4, CCR7, CD62Lhi, IL-7R (CD127) Surface phenotype αβ TCR, CD3, CD4, IL-12R, IFNγR, CXCR3 Surface phenotype αβ TCR, CD3, CD4, IL-23R, CCR6, IL-1R, Surface phenotype CCR7hi, CD44, CD62Lhi, TCR, CD3, Surface γδ TCR, CD3 phenotype Transcription THPOK Transcription factors T-bet, STAT4, STAT1 CD161 (human only) IL-7R (CD127), IL-15R Effector IFN , IL-17A, IL-17F, IL-22 factors Effector molecules secreted IFN , IL-2, LT Transcription factors RORγt, STAT3, RORα Transcription factors BCL-6, BCL-6B, MBD2, BMI1 γ γ α molecules Function Patrol through lymph nodes scanning peptide– Effector molecules secreted IL-17A, IL-17F, IL-21, IL-22, CCL20 Effector molecules IL-2, CD40L Function Promote protective immunity against intracellular pathogens. By secreting secreted MHC class II molecule complexes on APCs for IFN , they induce activation of macrophages and upregulation of iNOS, Function Promote protective immunity against extracellular bacteria and fungi, secreted Low levels IL-4, IFNγ, IL-17A γ Function Enriched at epithelial surfaces the presence of their cognate antigen. Following leading to the killing of intracellular pathogens such as Leishmania major, mainly at mucosal surfaces. Also promote autoimmune and inflammatory Function Preferentially reside in secondary lymphoid + and can have both pro- and activation by APCs, naive CD4 T cells Listeria monocytogenes and Mycobacterium spp. Their development is diseases. Generated in the presence of TGF and IL-6 and/or IL-21 and are organs, mounting recall responses to β anti-inflammatory functions, differentiate into effector or regulatory T cells; regulated by IL-12. maintained by IL-23 and IL-1. . Even though these cells lack activated naive T cells also give rise to memory immediate effector functions, they rapidly depending on the γδ TCR Other features Also express BATF, IκBζ, IRF4 and AHR transcription factors. Human T 17 cells T cells. H proliferate and differentiate into effector and the context. Have T 2 cell also produce IL-26. characteristics of both innate Other features CD45RA expressed by human cells. H T cells following antigen stimulation. Surface phenotype αβ TCR, CD3, CD4, IL-4R, IL-33R, CCR4, IL-17RB, CRTH2 and adaptive immunity. TH22 cell Other CD8+ αβ T cell Transcription factors GATA3, STAT6, DEC2, MAF Effector memory T cell IFNγ- and IL-17A-producing Surface phenotype αβ TCR, CD3, CD4, CCR10 low features cells are distinct populations hi Effector molecules secreted IL-4, IL-5, IL-13, IL-10 Surface phenotype CD62L , CD44, TCR, CD3, IL-7R (CD127), Surface phenotype αβ TCR, CD3, CD8, CCR7, CD62L , IL-7R (CD127) that can be distinguished by Transcription factors AHR IL-15R, CCR7low Transcription RUNX3 Function Promote humoral immune responses and host defence against extracellular CD27 and CCR6 expression. Effector molecules secreted IL-22 factors parasites. However, they can also potentiate allergic responses and asthma. Transcription factors BLIMP1 Innate immune recognition by Their development and maintenance is regulated by IL-4, IL-25 and IL-33. Function Identified in inflammatory skin diseases. Their role in host defence remains Function Patrol through lymph nodes scanning peptide– Effector molecules Rapid and high production of inflammatory expression of TLRs. unclear as this subset has only recently been characterized. Their identity as an MHC class I molecule complexes for the Other features IRF4 is also an important transcription factor. secreted cytokines independent T cell subset needs to be confirmed. presence of their cognate antigen. Following H Function Preferentially found in peripheral tissues. activation by APCs, they differentiate into T 9 cell They provide immediate protection upon H T cell CTLs and memory T cells. Surface phenotype αβ TCR, CD3, CD4 FH antigen challenge through, for example, the Surface phenotype TCR, CD3, CD4, CXCR5, SLAM, OX40L, CD40L, ICOS, IL-21R, PD1 rapid production of effector cytokines. Other features CD45RA expressed by human cells. Transcription factors PU.1 αβ Transcription factors BCL-6, STAT3 Effector molecules secreted IL-9, IL-10 Effector molecules secreted IL-21 Function Involved in host defence against extracellular parasites, primarily nematodes. Despite their production of anti-inflammatory IL-10, they Function These cells are involved in promotion of germinal centre responses and promote allergic inflammation. Their role in other inflammatory diseases provide help for class switching. still remains unclear as this subset has only recently been characterized. Other features SAP expression.

Abcam – Immunology products you can rely on! Abbreviations J, joining region; KGF, keratinocyte growth factor; L, ligand; LAG3, activation gene 3; Affiliations AHR, aryl hydrocarbon receptor; APC, antigen-presenting cell; BATF, basic leucine zipper LTα, lymphotoxin-α; MAF, musculoaponeurotic fibrosarcoma oncogene; MAIT, mucosal-associated Chen Dong and Gustavo J. Martinez are at the Abcam is a leading provider of research tools. We ship to over paper citations. Our customers also benefit from fast delivery, transcription factor, ATF-like; BCL-6, B cell 6; BLIMP1, B lymphocyte-induced maturation invariant T; MBD2, methyl-CpG-binding domain protein 2; MR1, MHC-related protein 1; NEDD4, Department of Immunology, M.D. Anderson Cancer protein 1; BTLA, B and T lymphocyte attenuator; CBL-B, Casitas B-lineage lymphoma B; neuronal precursor cell-expressed developmentally downregulated 4; NKT, natural killer T; Center and Graduate School of Biomedical Sciences, 115 countries from our offices in the UK, US, Japan and Hong Kong, multi-language customer service and technical support as well as a CCL, CC-chemokine ligand; CCR, CC-chemokine receptor; CRTH2, chemoattractant receptor- p27KIP1, p27 inhibitory protein 1; PD1, programmed cell death 1; PLZF, promyelocytic University of Texas Health Science Center at Houston, and offer customer service in English, French, German, Spanish, comprehensive product warranty. homologous molecule expressed on TH2 cells; CTL, cytotoxic T lymphocyte; CTLA4, cytotoxic leukaemia zinc-finger; R, receptor; ROR, retinoic acid receptor-related orphan receptor; RUNX3, Houston, Texas 77030, USA. Japanese and Chinese. T lymphocyte antigen 4; CXCR, CXC-chemokine receptor; EOMES, eomesodermin; FOX, Runt-related transcription factor 3; SAP, SLAM-associated protein; SLAM, signalling lymphocytic Our extensive catalog contains over 79,000 quality products, each forkhead box; GATA3, GATA-binding protein 3; GITR, glucocorticoid-induced TNF-receptor- activation molecule; SMAD, mothers against decapentaplegic homologue; STAT, signal transducer Edited by Yvonne Bordon; copyedited by Gemma Ryan; designed by Simon Bradbrook. related protein; GRAIL, gene related to anergy in lymphocytes; IκBζ, inhibitor of NF-κB-ζ; ICOS, and activator of transcription; TCR, T cell receptor; TFH, T follicular helper; TGFβ, transforming accompanied by a comprehensive and up-to-date datasheet that Visit our website today and find out how our products could help © 2010 Nature Publishing Group. inducible T cell co-stimulator; IFNγ, interferon-γ; IL, ; iNOS, inducible nitric oxide growth factor-β; THPOK, TH-inducing POZ/Kruppel-like factor; TH, T helper; TIM3, T cell includes customer reviews, frequently asked questions and scientific advance your research: www.abcam.com synthase; IRF4, interferon-regulatory factor 4; ITCH, itchy homologue E3 ubiquitin protein ligase; and mucin domain protein 3; TLR, Toll-like receptor; V, variable region. http://www.nature.com/reviews/posters/Tcellsubsets

nri_poster_sep10.indd 1 02/11/2011 15:26