Table 3 CD4+ T cell subsets

From: Guidelines for T cell nomenclature

Subset name

Markers and assays

Description

Human

Mouse

TH1 cell

CXCR3+, CCR4, CCR6, CXCR5, T-bet+, IFNγ+ when stimulated

T-bet+, IFNγ+ when stimulated

Activated or memory CD4+ T cells predisposed to express IFNγ, but not IL-4, IL-5 or IL-13

Depend on T-bet to develop

TH2 cell

CRTh2+, CXCR3, CCR4+, CCR6, CXCR5, GATA3+

IL-4+, IL-5+ and/or IL-13+ when stimulated

GATA3+

IL-4+, IL-5+ and/or IL-13+ when stimulated

Activated or memory CD4+ T cells predisposed to express IL-4, IL-5 and IL-13, but not IFNγ

Depend on GATA3 to develop

TH9 cell

CXCR3, CCR4+, CCR6, CXCR5, CCR8+, PU.1 and IL-9 when stimulated, PPARγ+ in skin

PU.1 and IL-9 when stimulated

Activated or memory CD4+ T cells predisposed to express IL-9

Depend on multiple factors to develop, including PU.1, IRF4 and BATF

TH17 cell

CXCR3, CCR4+/−, CCR6+, CXCR5, RORγt+, IL-17+ when stimulated

RORγt+, IL-17+ when stimulated

Activated or memory CD4+ T cells that are predisposed to secrete IL-17

Depend on RORγt to develop

CD4+ CTL

In vitro chromium release assay, granzyme B+, CCR7, CD27, may express CD95

Same as human (see left)

A CD4+ T cell that exhibits cytolytic activity

TFH cell (T follicular helper cell)

CXCR5+, BCL6+

Same as human (see left)

CD4+ T cells that promote B cell activation, differentiation, antibody production, somatic hypermutation, class-switching, and memory

Depend on BCL6 to develop

GC TFH cell (germinal centre TFH cell)

ND

BCL6hi, CXCR5hi, PD-1hi, ICOS+, FR4hi PSGL1low

A subset of TFH cells that reside within germinal centres (GCs) of lymphoid organs wherein they help select high-affinity B cells undergoing somatic hypermutation

MZ TFH cell (mantle zone TFH cell)

ND

BCL6low, CXCR5low, PD-1low, FR4lo, PSGL1hi

A subset of TFH cells that reside within mantle regions of B cell follicles

May be the precursors of GC TFH cells or GC TFH cells that migrate out of GCs back into the mantle zone

TFHM (T follicular helper memory) cell

CXCR4+, FOXP3

TCF1+, FR4+, P2RX7+, CXCR4+

Long-lived CD4+ TFH cells that putatively persist after antigen clearance

Regulatory T (Treg) cell

Foxp3+, CD25hi, CD127low, CTLA4+, GITR+

Same as human (see left)

A subset of CD4+ T cells that regulate immune responses and promote tolerance

Depend on FOXP3 to develop

tTreg cell (thymus-derived Treg cell)

FOXP3+, CCR7hi, CD45RA+, CD45RO

FOXP3+, CD62L+, CD44lo, neuropilin-1hi, helioshi

Treg cells that differentiate upon recognition of self-antigens during thymic development

Also referred to as natural (nTreg) cells

Difficult to discriminate from pTreg cells in humans

pTreg cell (peripherally derived Treg cell)

FOXP3+, CCR7hi, CD45RA+, CD45RO

FOXP3+, CD62L+, CD44lo, neuropilin-1lo, helioslow/int

Treg cells that differentiate upon recognition of antigens in peripheral tissues

Also referred to as induced Treg cells

Difficult to discriminate from tTreg cells in humans

eTreg cell (effector Treg cell)

FOXP3hi, CD45RO+, CCR8hi, ICOShi, IRF4+

FOXP3hi, CD62L, CD44hi, BLIMP1+, IL-10+, TGFβ+

tTreg or pTreg cells that have undergone further activation-induced differentiation to alter their migration status and gain capacity for secretion of suppressive cytokines

iTreg cell (in vitro-induced Treg cell)

ND

ND

CD4+ T cells that are induced to differentiate into Treg cells in vitro

TFR (T follicular regulatory) cells

CXCR5+, FOXP3+, GITR+, IL-10+

CXCR5+, PD-1+, BCL6+, FOXP3+, GITR+, IL-10+

A subset of Treg cells that are localized within B cell follicles or GCs

  1. CCR, CC-chemokine receptor; CTL, cytotoxic T lymphocyte; CXCR, CXC-chemokine receptor; IFNγ, interferon-γ; ND, not defined; TH, T helper.