Functional and Phenotypic Plasticity of CD4+ T Cell Subsets
Table 1
Characterization of CD4+ T cell subsets.
Th subset
Factors inducing lineage
STAT activated
Lineage-specifying transcription factor
Effector cytokines produced
Functions
Th1
IL-12 IL-27
STAT4, STAT1
T-bet
IFN, lymphotoxin, TNF
Cell-mediated immunity, delayed-type hypersensitivity responses, clearance of intracellular pathogens and tumor cells, opsonizing Ab production by B cell class-switching to IgG2a [3, 4, 7–9]
Th2
IL-4 Indoleamine 2,3-dioxygenase
STAT6
Gata-3 c-MAF
IL-4, IL-5, IL-13, IL-10
Humoral immunity, clearance of extracellular bacteria and worms, B cell class-switching to IgE, allergic responses [3, 4, 7, 10, 11]
Th9
IL-4 TGF
STAT6
BATF
IL-9, IL-10
Protection against parasitic worms/helminth infections [12, 13]
Th17
IL-6 MyD88 Low TGF IL-23
STAT3
RORT, RORα
IL-17, IL-17F, IL-6, IL-22, TNF, IL-10
Protection of mucosal surfaces, recruitment of neutrophils, clearance of Mycobacterium tuberculosis and Klebsiella pneumonia [3, 14–17]
Th22
IL-10R IL-6 TNFα
STAT3
Aryl hydrocarbon receptor
IL-22, IL-13, FGF, CCL15, CCL17, TNFα
Mucosal immunity, prevention of microbial translocation across epithelial surfaces, promotes wound repair. [18–21]
Th25
IL-4, IL-25
Unknown
Act1
IL-25, IL-4, IL-5, IL-13
Mucosal immunity, stimulates nonlymphoid cells to produce IL-4, limits Th1 and Th17 induced inflammation, CD4+ T cell memory (mouse) [12, 22]
TFH
Strong TCR signal, IL-12, CXCR5, IL-21, IL-4
STAT3
MAF (IL-21 transactivator)
IL-21, OX40, ICOS
Helps B cells produce high affinity, class-switched antibodies, guides migration into germinal centers [23, 24]
Treg (includes Tr1 and Th3 cells)
High TGF mTOR
STAT5
Foxp3
IL-10, TGF
Suppression of existing immune responses, maintains tolerance/protection against autoimmunity [15, 16, 25, 26]