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

Cytotoxic T cell
Surface
phenotype
Transcription
factors
Effector
molecules
secreted
Function

Other
features

TCR, CD3, CD8

Surface
phenotype
Transcription
factors
Function

EOMES, T-bet, BLIMP1

Perforin, granzyme, IFN

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

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

TCR

TCR
IL-7R

Other features

Other features

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

Effector
molecules
secreted

IL-10

Function

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

TCR
LAG3

BTLA

Cytokine
receptor

TCR

Surface phenotype
Transcription factors
Effector molecules secreted
Function

Inducible TReg cell

Surface phenotype
Transcription factors
Effector molecules secreted
Function

CD4

TCR

Chemokine
receptor

CD3

TCR, CD3, CD4, CD25, CTLA4, GITR

FOXP3, STAT5, FOXO1, FOXO3
IL-10, TGF, IL-35
Mediate immunosuppression and tolerogenic responses
through contact-dependent and -independent
mechanisms. These cells are generated in the thymus.

GITR

CD3

TCR, CD3, CD4, CD25, CTLA4, GITR

FOXP3, FOXO1, FOXO3, STAT5, SMAD2, SMAD3, SMAD4
IL-10, TGF
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, TGF and IL-2
are important for their differentiation.

Naive

CD8 T cell

Surface phenotype NK1.1, SLAMF1, SLAMF6, TGFR,

V14, J18 (mouse)
V24, J18 (human)
Transcription
PLZF
factors
Effector molecules IL-4, IFN, IL-17A
secreted
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 graftversus-host disease.
Other features
SAP expression. CD1-restricted TCR.
MAITcells express an invariant TCR -chain
(V33J19 in mice; V7.2J19 in humans).
MAITcells are MR1 restricted (not CD1 restricted)
but have similarities to NKT cells.

CD4
SLAMF1

CTLA4

CD3

CD25

TCR
CD44

NK1.1

IL-7R

CD3

TCR

SLAMF6

Surface
phenotype
Effector
molecules
secreted
Function

or TCR, CD3,
CD8, B220
IL-10, TGF

Intraepithelial lymphocytes
are found in the gut. They can
develop intra- or extrathymically. They express or
TCRs. TCR+ cells express
KGF, whereas TCR+ cells do
not. Most TCRs are
enriched for self-reactivity.
They require 2 microglobulindependent MHC class I
expression for their generation
and/or homeostasis. They can
have regulatory functions
through the production of
IL-10 and TGF.

TCR
TGFR

TCR

CD3

CD8
B220

CD3
CCR7

Cytotoxic

Exhausted

Anergic

Helper

TCR, CD3, CD4, CCR7, CD62Lhi, IL-7R (CD127)

THPOK
Patrol through lymph nodes scanning peptide
MHC classII molecule complexes on APCs for
the presence of their cognate antigen. Following
activation by APCs, naive CD4+ Tcells
differentiate into effector or regulatory Tcells;
activated naive T cells also give rise to memory
T cells.
CD45RA expressed by human cells.

TCR, CD3, CD8, CCR7, CD62Lhi, IL-7R (CD127)

RUNX3
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
CTLsand memory T cells.
CD45RA expressed by human cells.

Abcam - Immunology antibodies you can rely on!

Abcam is a leading supplier of primary and secondary antibodies to researchers
worldwide. We ship to over 100 countries from our offices in the UK, US, Japan and
Hong Kong, and offer customer service in English, French, German and Japanese.
Our catalog of over 60,000 products comprises antibodies, proteins, kits, lysates and
slides. We have more than 15,000 products in the immunology field including:
Adaptive and innate immunity
Cell type markers
Immunoglobulins
Immune system diseases
Secreted molecules
Transplantation

Surface phenotype
Transcription factors
Effector molecules secreted
Function

TCR, CD3, CD4, IL-12R, IFNR, CXCR3

T-bet, STAT4, STAT1
IFN, IL-2, LT
Promote protective immunity against intracellular pathogens. By secreting
IFN, 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.

Other features

TCR, CD3, CD4, IL-4R, IL-33R, CCR4, IL-17RB, CRTH2

GATA3, STAT6, DEC2, MAF
IL-4, IL-5, IL-13, IL-10
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.
IRF4 is also an important transcription factor.

TH9 cell
Surface phenotype
Transcription factors
Effector molecules secreted
Function

Surface phenotype
Transcription factors
Effector molecules secreted
Function

Other features

TH2 cell
Surface phenotype
Transcription factors
Effector molecules secreted
Function

Regulatory

Memory

TH17 cell

TH1 cell

CD8+ T cell
Surface phenotype
Transcription
factors
Function

GRAIL, CBL-B, ITCH, NEDD4

TIM3 1B11

CD3

CD4+ T cell
Surface phenotype
Transcription
factors
Function

Surface
TCR, CD3, CD4
phenotype
Transcription Not known
factors

CCR7

60m
40m

CD8 PD1

CD62L

CD3

TCR, CD3, BTLA

NKT cell

Natural TReg cell

CD8

CD3

80m

Surface
phenotype
Effector
factors
Function

CD3, CD8, PD1,

TIM3, 1B11, LAG3
BLIMP1

Other
features

100m

TR1 cell

Anergic T cell

Exhausted T cell

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.

TCR, CD3, CD4

PU.1
IL-9, IL-10
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.

We are rapidly developing and expanding our product range, looking for new targets and
improving our existing antibodies. To help us with this, we actively attend, support and help
organize conferences on immunology research. Find out more on our immunology resource page:
[Link]/immunology.
Quality and honesty are our top priorities. Our Abpromise offers 100% scientific and customer support
of any product purchased from Abcam or one of our authorized distributors. If our products do not
perform as described on the datasheet, notify us within 120 days of delivery so we can help you or offer
a replacement or refund. Our web-based catalog allows daily updates and far more information than
any printed catalog including, customer reviews, technical enquiries and links to publication references.
Visit our website today and see for yourself: [Link].

Central memory T cell

TCR, CD3, CD4, IL-23R, CCR6, IL-1R,
CD161 (human only)
RORt, STAT3, ROR
IL-17A, IL-17F, IL-21, IL-22, CCL20
Promote protective immunity against extracellular bacteria and fungi,
mainly at mucosal surfaces. Also promote autoimmune and inflammatory
diseases. Generated in the presence of TGF and IL-6 and/or IL-21 and are
maintained by IL-23 and IL-1.
Also express BATF, IB, IRF4 and AHR transcription factors. Human TH17 cells
also produce IL-26.

TH22 cell
Surface phenotype
Transcription factors
Effector molecules secreted
Function

TCR, CD3, CD4, CCR10

AHR
IL-22
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.

TFH cell
Surface phenotype
Transcription factors
Effector molecules secreted
Function
Other features

TCR, CD3, CD4, CXCR5, SLAM, OX40L, CD40L, ICOS, IL-21R, PD1
BCL-6, STAT3
IL-21
These cells are involved in promotion of germinal centre responses and
provide help for Bcell class switching.
SAP expression.

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 receptorhomologous molecule expressed on TH2 cells; CTL, cytotoxic T lymphocyte; CTLA4, cytotoxic
Tlymphocyte antigen 4; CXCR, CXC-chemokine receptor; EOMES, eomesodermin; FOX,
forkhead box; GATA3, GATA-binding protein 3; GITR, glucocorticoid-induced TNF-receptorrelated protein; GRAIL, gene related to anergy in lymphocytes; IB, inhibitor of NF-B-; ICOS,
inducible T cell co-stimulator; IFN, interferon-; IL, interleukin; iNOS, inducible nitric oxide
synthase; IRF4, interferon-regulatory factor 4; ITCH, itchy homologue E3ubiquitin protein ligase;
2015 Macmillan Publishers Limited. All rights reserved

Surface phenotype
Transcription factors
Effector molecules
secreted
Function

CCR7hi, CD44, CD62Lhi, TCR, CD3,

IL-7R (CD127), IL-15R
BCL-6, BCL-6B, MBD2, BMI1
IL-2, CD40L
Low levels IL-4, IFN, IL-17A
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
Tcells following antigen stimulation.

Effector memory T cell

Surface phenotype
Transcription factors
Effector molecules
secreted
Function

CD8

NKT

CD62Llow, CD44, TCR, CD3, IL-7R (CD127),

IL-15R, CCR7low
BLIMP1
Rapid and high production of inflammatory
cytokines
Preferentially found in peripheral tissues.
They provide immediate protection upon
antigen challenge through, for example, the
rapid production of effector cytokines.

J, joining region; KGF, keratinocyte growth factor; L, ligand; LAG3,lymphocyte activation gene 3;
LT, lymphotoxin-; MAF, musculoaponeurotic fibrosarcoma oncogene; MAIT, mucosal-associated
invariant T; MBD2, methyl-CpG-binding domain protein 2; MR1, MHC-related protein1; NEDD4,
neuronal precursor cell-expressed developmentally downregulated 4; NKT, natural killer T;
p27KIP1, p27 kinase inhibitory protein 1; PD1, programmed cell death1; 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, Tfollicular helper; TGF, transforming
growth factor-; THPOK, TH-inducing POZ/Kruppel-like factor; TH, T helper; TIM3, Tcell
immunoglobulin domain and mucin domain protein 3; TLR, Toll-like receptor; V, variable region.

T cell
Surface
phenotype
Effector
molecules
secreted
Function

Other
features

TCR, CD3
IFN, IL-17A, IL-17F, IL-22

Enriched at epithelial surfaces

and can have both pro- and
anti-inflammatory functions,
depending on the TCR
and the context. Have
characteristics of both innate
and adaptive immunity.
IFN- and IL-17A-producing
cells are distinct populations
that can be distinguished by
CD27 and CCR6 expression.
Innate immune recognition by
expression of TLRs.

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.
[Link]