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]