T Cells the usual subsets - Abcamdocs.abcam.com/pdf/immunology/t_cells_the_usual_subsets.pdf · TCR...

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TCR TCR TCR BTLA CCR7 CD62L CD3 IL-7R IL-7R NK1.1 SLAMF1 TCR SLAMF6 TGFβR CD3 CD3 CD3 CD8 CD8 PD1 TIM3 1B11 LAG3 TCR CD3 Cytokine receptor Chemokine receptor CD4 CCR7 TCR CD3 GITR CD4 CTLA4 CD25 TCR CD3 CD44 TCR CD8αα CD3 B220 γδ TCR CD3 8’0μm 10’0μm 6’0μm 4’0μm 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 through cell contact-dependent mechanisms. Many T cell subsets have been characterized. Although effector T cells were originally considered to be terminally differentiated, a growing body of evidence has challenged this view and suggested that the phenotype of effector T cells is not completely fixed but is more flexible or plastic. T cells can have ‘mixed’ phenotypes (that is, have characteristics usually associated with more than one T cell subset) and can interconvert from one subset phenotype to another, although instructive signalling can lead to long-term fixation of cytokine memory. T cell plasticity can be important for adaptation of immune responses in different microenvironments and might be particularly relevant for host defence against pathogens that colonize different tissues. Distinct T cell subsets, or differentiation states, can be identified based on the cell surface markers expressed and/or the effector molecules produced by a particular T cell population. This Poster summarizes our current understanding of the surface markers, transcriptional regulators, effector molecules and functions of the different T cell subsets that participate in immune responses. Further knowledge of how these T cell subsets are regulated and cooperate with each other will provide us with better tools to treat immune-related diseases. Abcam – Immunology products you can rely on! Abbreviations AHR, aryl hydrocarbon receptor; APC, antigen-presenting cell; BATF, basic leucine zipper transcription factor, ATF-like; BCL-6, B cell lymphoma 6; BLIMP1, B lymphocyte-induced maturation protein 1; BTLA, B and T lymphocyte attenuator; CBL-B, Casitas B-lineage lymphoma B; CCL, CC-chemokine ligand; CCR, CC-chemokine receptor; CRTH2, chemoattractant receptor- homologous molecule expressed on T H 2 cells; CTL, cytotoxic T lymphocyte; CTLA4, cytotoxic T lymphocyte antigen 4; CXCR, CXC-chemokine receptor; EOMES, eomesodermin; FOX, forkhead box; GATA3, GATA-binding protein 3; GITR, glucocorticoid-induced TNF-receptor- related protein; GRAIL, gene related to anergy in lymphocytes; IκBζ, inhibitor of NF-κB-ζ; ICOS, inducible T cell co-stimulator; IFNγ, interferon-γ; IL, interleukin; iNOS, inducible nitric oxide synthase; IRF4, interferon-regulatory factor 4; ITCH, itchy homologue E3 ubiquitin protein ligase; Affiliations Chen Dong and Gustavo J. Martinez are at the Department of Immunology, M.D. Anderson Cancer Center and Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA. Edited by Yvonne Bordon; copyedited by Gemma Ryan; designed by Simon Bradbrook. © 2010 Nature Publishing Group. http://www.nature.com/reviews/posters/Tcellsubsets Abcam is a leading provider of protein research tools. We ship to over 115 countries from our offices in the UK, US, Japan and Hong Kong, and offer customer service in English, French, German, Spanish, Japanese and Chinese. Our extensive catalog contains over 79,000 quality products, each accompanied by a comprehensive and up-to-date datasheet that includes customer reviews, frequently asked questions and scientific paper citations. Our customers also benefit from fast delivery, multi-language customer service and technical support as well as a comprehensive product warranty. Visit our website today and find out how our products could help advance your research: www.abcam.com J, joining region; KGF, keratinocyte growth factor; L, ligand; LAG3, lymphocyte activation gene 3; LTα, lymphotoxin-α; MAF, musculoaponeurotic fibrosarcoma oncogene; MAIT, mucosal-associated invariant T; MBD2, methyl-CpG-binding domain protein 2; MR1, MHC-related protein 1; NEDD4, neuronal precursor cell-expressed developmentally downregulated 4; NKT, natural killer T; p27KIP1, p27 kinase inhibitory protein 1; PD1, programmed cell death 1; PLZF, promyelocytic leukaemia zinc-finger; R, receptor; ROR, retinoic acid receptor-related orphan receptor; RUNX3, Runt-related transcription factor 3; SAP, SLAM-associated protein; SLAM, signalling lymphocytic activation molecule; SMAD, mothers against decapentaplegic homologue; STAT, signal transducer and activator of transcription; TCR, T cell receptor; T FH , T follicular helper; TGFβ, transforming growth factor-β; THPOK, T H -inducing POZ/Kruppel-like factor; T H , T helper; TIM3, T cell immunoglobulin domain and mucin domain protein 3; TLR, Toll-like receptor; V, variable region. IMMUNOLOGY CD4 + αβ T cell Surface phenotype αβ TCR, CD3, CD4, CCR7, CD62L hi , IL-7R (CD127) Transcription factors THPOK Function Patrol through lymph nodes scanning peptide– MHC class II molecule complexes on APCs for the presence of their cognate antigen. Following activation by APCs, naive CD4 + T cells differentiate into effector or regulatory T cells; activated naive T cells also give rise to memory T cells. Other features CD45RA expressed by human cells. Natural T Reg cell Surface phenotype αβ TCR, CD3, CD4, CD25, CTLA4, GITR Transcription factors FOXP3, STAT5, FOXO1, FOXO3 Effector molecules secreted IL-10, TGFβ, IL-35 Function Mediate immunosuppression and tolerogenic responses through contact-dependent and -independent mechanisms. These cells are generated in the thymus. Central memory T cell Surface phenotype CCR7 hi , CD44, CD62L hi , TCR, CD3, IL-7R (CD127), IL-15R Transcription factors BCL-6, BCL-6B, MBD2, BMI1 Effector molecules secreted IL-2, CD40L Low levels IL-4, IFNγ, IL-17A Function Preferentially reside in secondary lymphoid organs, mounting recall responses to antigens. Even though these cells lack immediate effector functions, they rapidly proliferate and differentiate into effector T cells following antigen stimulation. Inducible T Reg cell Surface phenotype αβ TCR, CD3, CD4, CD25, CTLA4, GITR Transcription factors FOXP3, FOXO1, FOXO3, STAT5, SMAD2, SMAD3, SMAD4 Effector molecules secreted IL-10, TGFβ Function Promote immunosuppression and tolerance by contact-dependent and -independent mechanisms. These cells are generated from naive T cells in the periphery and, at least in some cases, TGFβ and IL-2 are important for their differentiation. Effector memory T cell Surface phenotype CD62L low , CD44, TCR, CD3, IL-7R (CD127), IL-15R, CCR7 low Transcription factors BLIMP1 Effector molecules secreted Rapid and high production of inflammatory cytokines Function Preferentially found in peripheral tissues. They provide immediate protection upon antigen challenge through, for example, the rapid production of effector cytokines. T H 1 cell Surface phenotype αβ TCR, CD3, CD4, IL-12R, IFNγR, CXCR3 Transcription factors T-bet, STAT4, STAT1 Effector molecules secreted IFNγ, IL-2, LTα Function Promote protective immunity against intracellular pathogens. By secreting IFNγ, they induce activation of macrophages and upregulation of iNOS, leading to the killing of intracellular pathogens such as Leishmania major, Listeria monocytogenes and Mycobacterium spp. Their development is regulated by IL-12. T H 2 cell Surface phenotype αβ TCR, CD3, CD4, IL-4R, IL-33R, CCR4, IL-17RB, CRTH2 Transcription factors GATA3, STAT6, DEC2, MAF Effector molecules secreted IL-4, IL-5, IL-13, IL-10 Function Promote humoral immune responses and host defence against extracellular parasites. However, they can also potentiate allergic responses and asthma. Their development and maintenance is regulated by IL-4, IL-25 and IL-33. Other features IRF4 is also an important transcription factor. T H 9 cell Surface phenotype αβ TCR, CD3, CD4 Transcription factors PU.1 Effector molecules secreted IL-9, IL-10 Function Involved in host defence against extracellular parasites, primarily nematodes. Despite their production of anti-inflammatory IL-10, they promote allergic inflammation. Their role in other inflammatory diseases still remains unclear as this subset has only recently been characterized. T H 22 cell Surface phenotype αβ TCR, CD3, CD4, CCR10 Transcription factors AHR Effector molecules secreted IL-22 Function Identified in inflammatory skin diseases. Their role in host defence remains unclear as this subset has only recently been characterized. Their identity as an independent T H cell subset needs to be confirmed. T H 17 cell Surface phenotype αβ TCR, CD3, CD4, IL-23R, CCR6, IL-1R, CD161 (human only) Transcription factors RORγt, STAT3, RORα Effector molecules secreted IL-17A, IL-17F, IL-21, IL-22, CCL20 Function Promote protective immunity against extracellular bacteria and fungi, mainly at mucosal surfaces. Also promote autoimmune and inflammatory diseases. Generated in the presence of TGFβ and IL-6 and/or IL-21 and are maintained by IL-23 and IL-1. Other features Also express BATF, IκBζ, IRF4 and AHR transcription factors. Human T H 17 cells also produce IL-26. CD8 + αβ T cell Surface phenotype αβ TCR, CD3, CD8, CCR7, CD62L hi , IL-7R (CD127) Transcription factors RUNX3 Function Patrol through lymph nodes scanning peptide– MHC class I molecule complexes for the presence of their cognate antigen. Following activation by APCs, they differentiate into CTLs and memory T cells. Other features CD45RA expressed by human cells. Cytotoxic T cell Surface phenotype αβ TCR, CD3, CD8 Transcription factors EOMES, T-bet, BLIMP1 Effector molecules secreted Perforin, granzyme, IFNγ Function Cytotoxic; kill infected and transformed cells and thereby protect the host from viral infections and cancer. Direct killing is mediated by secretion of perforin and granzymes, which cause apoptosis of target cells. Other features In humans, mainly CD45RO + . Some terminally differentiated CTLs in humans re-express CD45RA. Exhausted T cell Surface phenotype CD3, CD8, PD1, TIM3, 1B11, LAG3 Transcription factors BLIMP1 Function Generated in response to chronic antigen- mediated TCR stimulation. These cells express inhibitory receptors and lack effector cytokine production; they therefore fail to mount effective antiviral immune responses. Anergic T cell Surface phenotype αβ TCR, CD3, BTLA Effector factors GRAIL, CBL-B, ITCH, NEDD4 Function These cells are generated following TCR activation in the absence of co-stimulatory signals, which leads them to become unresponsive to subsequent stimulatory signals. They are functionally inactive cells and fail to proliferate or produce IL-2. Their generation may be important for avoiding autoimmune responses. Other features Increased expression of p27KIP1, which leads to cell cycle arrest. T FH cell Surface phenotype αβ TCR, CD3, CD4, CXCR5, SLAM, OX40L, CD40L, ICOS, IL-21R, PD1 Transcription factors BCL-6, STAT3 Effector molecules secreted IL-21 Function These cells are involved in promotion of germinal centre responses and provide help for B cell class switching. Other features SAP expression. T R 1 cell Surface phenotype αβ TCR, CD3, CD4 Transcription factors Not known Effector molecules secreted IL-10 Function Immunosuppression mediated by IL-10 production. These cells are generated from naive T cells in the presence of TGFβ and IL-27 or in the presence of the immuno- suppressive drugs vitamin D3 and dexamethasone. NKT cell Surface phenotype NK1.1, SLAMF1, SLAMF6, TGFβR, Vα14, Jα18 (mouse) Vα24, Jα18 (human) Transcription factors PLZF Effector molecules secreted IL-4, IFNγ, IL-17A Function Can have both pro- and anti-inflammatory functions. Have been shown to modulate immune responses in several different settings, including cancer, autoimmunity, allergy, infection and graft- versus-host disease. Other features SAP expression. CD1-restricted TCR. MAIT cells express an invariant TCR α-chain (Vα33Jα19 in mice; Vα7.2Jα19 in humans). MAIT cells are MR1 restricted (not CD1 restricted) but have similarities to NKT cells. γδ T cell Surface phenotype γδ TCR, CD3 Effector molecules secreted IFNγ, IL-17A, IL-17F, IL-22 Function Enriched at epithelial surfaces and can have both pro- and anti-inflammatory functions, depending on the γδ TCR and the context. Have characteristics of both innate and adaptive immunity. Other features IFNγ- and IL-17A-producing cells are distinct populations that can be distinguished by CD27 and CCR6 expression. Innate immune recognition by expression of TLRs. CD8αα T cell Surface phenotype αβ or γδ TCR, CD3, CD8αα, B220 Effector molecules secreted IL-10, TGFβ Function Intraepithelial lymphocytes are found in the gut. They can develop intra- or extra- thymically. They express αβ or γδ TCRs. γδ TCR + cells express KGF, whereas αβ TCR + cells do not. Most αβ TCRs are enriched for self-reactivity. They require β 2 microglobulin- dependent MHC class I expression for their generation and/or homeostasis. They can have regulatory functions through the production of IL-10 and TGFβ. Naive Cytotoxic Exhausted Anergic Helper Regulatory Memory NKT CD8αα γδ nri_poster_sep10.indd 1 02/11/2011 15:26

Transcript of T Cells the usual subsets - Abcamdocs.abcam.com/pdf/immunology/t_cells_the_usual_subsets.pdf · TCR...

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T cells: the usual subsetsChen Dong and Gustavo J. Martinez

T cells have important roles in immune responses and function by directly secreting soluble mediators or through cell contact-dependent mechanisms. Many T cell subsets have been characterized. Although effector T cells were originally considered to be terminally differentiated, a growing body of evidence has challenged this view and suggested that the phenotype of effector T cells is not completely fixed but is more flexible or plastic. T cells can have ‘mixed’ phenotypes (that is, have characteristics usually associated with more than one T cell subset) and can interconvert from one subset phenotype to another, although instructive signalling can lead to long-term fixation of cytokine memory. T cell plasticity can be

important for adaptation of immune responses in different microenvironments and might be particularly relevant for host defence against pathogens that colonize different tissues. Distinct T cell subsets, or differentiation states, can be identified based on the cell surface markers expressed and/or the effector molecules produced by a particular T cell population. This Poster summarizes our current understanding of the surface markers, transcriptional regulators, effector molecules and functions of the different T cell subsets that participate in immune responses. Further knowledge of how these T cell subsets are regulated and cooperate with each other will provide us with better tools to treat immune-related diseases.

Abcam – Immunology products you can rely on! Abbreviations AHR, aryl hydrocarbon receptor; APC, antigen-presenting cell; BATF, basic leucine zipper transcription factor, ATF-like; BCL-6, B cell lymphoma 6; BLIMP1, B lymphocyte-induced maturation protein 1; BTLA, B and T lymphocyte attenuator; CBL-B, Casitas B-lineage lymphoma B; CCL, CC-chemokine ligand; CCR, CC-chemokine receptor; CRTH2, chemoattractant receptor-homologous molecule expressed on TH2 cells; CTL, cytotoxic T lymphocyte; CTLA4, cytotoxic T lymphocyte antigen 4; CXCR, CXC-chemokine receptor; EOMES, eomesodermin; FOX, forkhead box; GATA3, GATA-binding protein 3; GITR, glucocorticoid-induced TNF-receptor-related protein; GRAIL, gene related to anergy in lymphocytes; IκBζ, inhibitor of NF-κB-ζ; ICOS, inducible T cell co-stimulator; IFNγ,  interferon-γ; IL, interleukin; iNOS, inducible nitric oxide synthase; IRF4, interferon-regulatory factor 4; ITCH, itchy homologue E3 ubiquitin protein ligase;

AffiliationsChen Dong and Gustavo J. Martinez are at the Department of Immunology, M.D. Anderson Cancer Center and Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.

Edited by Yvonne Bordon; copyedited by Gemma Ryan; designed by Simon Bradbrook.© 2010 Nature Publishing Group.http://www.nature.com/reviews/posters/Tcellsubsets

Abcam is a leading provider of protein research tools. We ship to over 115 countries from our offices in the UK, US, Japan and Hong Kong, and offer customer service in English, French, German, Spanish, Japanese and Chinese.

Our extensive catalog contains over 79,000 quality products, each accompanied by a comprehensive and up-to-date datasheet that includes customer reviews, frequently asked questions and scientific

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J, joining region; KGF, keratinocyte growth factor; L, ligand; LAG3, lymphocyte activation gene 3; LTα, lymphotoxin-α; MAF, musculoaponeurotic fibrosarcoma oncogene; MAIT, mucosal-associated invariant T; MBD2, methyl-CpG-binding domain protein 2; MR1, MHC-related protein 1; NEDD4, neuronal precursor cell-expressed developmentally downregulated 4; NKT, natural killer T; p27KIP1, p27 kinase inhibitory protein 1; PD1, programmed cell death 1; PLZF, promyelocytic leukaemia zinc-finger; R, receptor; ROR, retinoic acid receptor-related orphan receptor; RUNX3, Runt-related transcription factor 3; SAP, SLAM-associated protein; SLAM, signalling lymphocytic activation molecule; SMAD, mothers against decapentaplegic homologue; STAT, signal transducer and activator of transcription; TCR, T cell receptor; TFH, T follicular helper; TGFβ, transforming growth factor-β; THPOK, TH-inducing POZ/Kruppel-like factor; TH, T helper; TIM3, T cell immunoglobulin domain and mucin domain protein 3; TLR, Toll-like receptor; V, variable region.

IMMUNOLOGY

CD4+ αβ T cellSurface phenotype αβ TCR, CD3, CD4, CCR7, CD62Lhi, IL-7R (CD127)Transcription factors

THPOK

Function Patrol through lymph nodes scanning peptide–MHC class II molecule complexes on APCs for the presence of their cognate antigen. Following activation by APCs, naive CD4+ T cells differentiate into effector or regulatory T cells; activated naive T cells also give rise to memory T cells.

Other features CD45RA expressed by human cells.

Natural TReg cellSurface phenotype αβ TCR, CD3, CD4, CD25, CTLA4, GITRTranscription factors FOXP3, STAT5, FOXO1, FOXO3Effector molecules secreted IL-10, TGFβ, IL-35Function Mediate immunosuppression and tolerogenic responses

through contact-dependent and -independent mechanisms. These cells are generated in the thymus.

Central memory T cellSurface phenotype CCR7hi, CD44, CD62Lhi, TCR, CD3,

IL-7R (CD127), IL-15RTranscription factors BCL-6, BCL-6B, MBD2, BMI1Effector molecules secreted

IL-2, CD40LLow levels IL-4, IFNγ, IL-17A

Function Preferentially reside in secondary lymphoid organs, mounting recall responses to antigens. Even though these cells lack immediate effector functions, they rapidly proliferate and differentiate into effector T cells following antigen stimulation.

Inducible TReg cellSurface phenotype αβ TCR, CD3, CD4, CD25, CTLA4, GITRTranscription factors FOXP3, FOXO1, FOXO3, STAT5, SMAD2, SMAD3, SMAD4Effector molecules secreted IL-10, TGFβ Function Promote immunosuppression and tolerance by

contact-dependent and -independent mechanisms. These cells are generated from naive T cells in the periphery and, at least in some cases, TGFβ and IL-2 are important for their differentiation.

Effector memory T cellSurface phenotype CD62Llow, CD44, TCR, CD3, IL-7R (CD127),

IL-15R, CCR7low

Transcription factors BLIMP1Effector molecules secreted

Rapid and high production of inflammatory cytokines

Function Preferentially found in peripheral tissues. They provide immediate protection upon antigen challenge through, for example, the rapid production of effector cytokines.

TH1 cellSurface phenotype αβ TCR, CD3, CD4, IL-12R, IFNγR, CXCR3Transcription factors T-bet, STAT4, STAT1Effector molecules secreted IFNγ, IL-2, LTαFunction Promote protective immunity against intracellular pathogens. By secreting

IFNγ, they induce activation of macrophages and upregulation of iNOS, leading to the killing of intracellular pathogens such as Leishmania major, Listeria monocytogenes and Mycobacterium spp. Their development is regulated by IL-12.

TH2 cellSurface phenotype αβ TCR, CD3, CD4, IL-4R, IL-33R, CCR4, IL-17RB, CRTH2Transcription factors GATA3, STAT6, DEC2, MAFEffector molecules secreted IL-4, IL-5, IL-13, IL-10Function Promote humoral immune responses and host defence against extracellular

parasites. However, they can also potentiate allergic responses and asthma. Their development and maintenance is regulated by IL-4, IL-25 and IL-33.

Other features IRF4 is also an important transcription factor.

TH9 cellSurface phenotype αβ TCR, CD3, CD4Transcription factors PU.1Effector molecules secreted IL-9, IL-10Function Involved in host defence against extracellular parasites, primarily

nematodes. Despite their production of anti-inflammatory IL-10, they promote allergic inflammation. Their role in other inflammatory diseases still remains unclear as this subset has only recently been characterized.

TH22 cellSurface phenotype αβ TCR, CD3, CD4, CCR10Transcription factors AHREffector molecules secreted IL-22Function Identified in inflammatory skin diseases. Their role in host defence remains

unclear as this subset has only recently been characterized. Their identity as an independent TH cell subset needs to be confirmed.

TH17 cellSurface phenotype αβ TCR, CD3, CD4, IL-23R, CCR6, IL-1R,

CD161 (human only)Transcription factors RORγt, STAT3, RORαEffector molecules secreted IL-17A, IL-17F, IL-21, IL-22, CCL20Function Promote protective immunity against extracellular bacteria and fungi,

mainly at mucosal surfaces. Also promote autoimmune and inflammatory diseases. Generated in the presence of TGFβ and IL-6 and/or IL-21 and are maintained by IL-23 and IL-1.

Other features Also express BATF, IκBζ, IRF4 and AHR transcription factors. Human TH17 cells also produce IL-26.

CD8+ αβ T cellSurface phenotype αβ TCR, CD3, CD8, CCR7, CD62Lhi, IL-7R (CD127)Transcription factors

RUNX3

Function Patrol through lymph nodes scanning peptide–MHC class I molecule complexes for the presence of their cognate antigen. Following activation by APCs, they differentiate into CTLs and memory T cells.

Other features CD45RA expressed by human cells.

Cytotoxic T cellSurface phenotype

αβ TCR, CD3, CD8

Transcription factors

EOMES, T-bet, BLIMP1

Effector molecules secreted

Perforin, granzyme, IFNγ

Function Cytotoxic; kill infected and transformed cells and thereby protect the host from viral infections and cancer. Direct killing is mediated by secretion of perforin and granzymes, which cause apoptosis of target cells.

Other features

In humans, mainly CD45RO+. Some terminally differentiated CTLs in humans re-express CD45RA.

Exhausted T cellSurface phenotype

CD3, CD8, PD1, TIM3, 1B11, LAG3

Transcription factors

BLIMP1

Function Generated in response to chronic antigen-mediated TCR stimulation. These cells express inhibitory receptors and lack effector cytokine production; they therefore fail to mount effective antiviral immune responses.

Anergic T cellSurface phenotype

αβ TCR, CD3, BTLA

Effector factors

GRAIL, CBL-B, ITCH, NEDD4

Function These cells are generated following TCR activation in the absence of co-stimulatory signals, which leads them to become unresponsive to subsequent stimulatory signals. They are functionally inactive cells and fail to proliferate or produce IL-2. Their generation may be important for avoiding autoimmune responses.

Other features

Increased expression of p27KIP1, which leads to cell cycle arrest.

TFH cellSurface phenotype αβ TCR, CD3, CD4, CXCR5, SLAM, OX40L, CD40L, ICOS, IL-21R, PD1Transcription factors BCL-6, STAT3Effector molecules secreted IL-21Function These cells are involved in promotion of germinal centre responses and

provide help for B cell class switching.Other features SAP expression.

TR1 cellSurface phenotype

αβ TCR, CD3, CD4

Transcription factors

Not known

Effector molecules secreted

IL-10

Function Immunosuppression mediated by IL-10 production. These cells are generated from naive T cells in the presence of TGFβ and IL-27 or in the presence of the immuno-suppressive drugs vitamin D3 and dexamethasone.

NKT cellSurface phenotype NK1.1, SLAMF1, SLAMF6, TGFβR,

Vα14, Jα18 (mouse)Vα24, Jα18 (human)

Transcription factors

PLZF

Effector molecules secreted

IL-4, IFNγ, IL-17A

Function Can have both pro- and anti-inflammatory functions. Have been shown to modulate immune responses in several different settings, including cancer, autoimmunity, allergy, infection and graft-versus-host disease.

Other features SAP expression. CD1-restricted TCR. MAIT cells express an invariant TCR α-chain (Vα33Jα19 in mice; Vα7.2Jα19 in humans). MAIT cells are MR1 restricted (not CD1 restricted) but have similarities to NKT cells.

γδ T cellSurface phenotype

γδ TCR, CD3

Effector molecules secreted

IFNγ, IL-17A, IL-17F, IL-22

Function Enriched at epithelial surfaces and can have both pro- and anti-inflammatory functions, depending on the γδ TCR and the context. Have characteristics of both innate and adaptive immunity.

Other features

IFNγ- and IL-17A-producing cells are distinct populations that can be distinguished by CD27 and CCR6 expression. Innate immune recognition by expression of TLRs.

CD8αα T cellSurface phenotype

αβ or γδ TCR, CD3, CD8αα, B220

Effector molecules secreted

IL-10, TGFβ

Function Intraepithelial lymphocytes are found in the gut. They can develop intra- or extra-thymically. They express αβ or γδ TCRs. γδ TCR+ cells express KGF, whereas αβ TCR+ cells do not. Most αβ TCRs are enriched for self-reactivity. They require β2 microglobulin-dependent MHC class I expression for their generation and/or homeostasis. They can have regulatory functions through the production of IL-10 and TGFβ.

Naive Cytotoxic Exhausted Anergic Helper Regulatory Memory NKT CD8ααγδ

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