Follicular helper T lymphocytes in health and disease

Table 1 Follicular helper T lymphocytes markers

Marker	Human TFH		NaïveCD4+ T cell	ActivatedNon-TFH CD4+
	TFH	GC TFH
CXCR5	+	++	-	-
Ascl2	?	++	?	?
Bcl-6	+	++	-	-
Blimp-1	-	-	+/-	++/variable
PD-1	+	++	-	Variable
ICOS	+	++	-	Variable
SAP	+	++	+	+
IL-21	+	++	-	Variable
IL-4	-/+	++	-	Th2+
CCR7	-/+	-	++	Variable

T_FH: Follicular helper T lymphocytes; GC: Germinal center; CXCR5: Chemokine (C-X-C motif) receptor 5; Ascl2: Achaete-scute homologue 2; Bcl-6: B cell lymphoma 6; Blimp-1: B lymphocyte-induced maturation protein 1; PD-1: Programmed cell death-1; ICOS: Inducible costimulator; SAP: Signaling adaptor SLAM-associated protein; IL: Interleukin; CCR7: Chemokine (C-C motif) receptor 7; Th: T helper.

Table 2 Heterogeneity of follicular helper T lymphocytes in relation to other T helper cells

	Markers
	CD4	CXCR5	CXCR3	CCR6	Foxp3
Th1 TFH	+	+	+	-	-
Th2 TFH	+	+	-	-	-
Th17 TFH	+	+	-	+	-
TFR TFH	+	+	-	-	+

T_FH: Follicular helper T lymphocytes; Th: T helper; CXCR5: Chemokine (C-X-C motif) receptor 5; CXCR3: Chemokine (C-X-C motif) receptor 3; CCR6: Chemokine (C-C motif) receptor 6; Foxp3: Forkhead box P3; T_FR: Foxp3+ CXCR5⁺ Bcl-6⁺ regulatory T cells.

Table 3 Follicular helper T lymphocytes in autoimmune diseases

Disease	TFH	Ref.
SLE	Increased CXCR5 and function	[46-48]
Myasthenia gravis	Increased CXCR5 and function	[49]
RA	Increased CXCR5 and function	[1,50]
Juvenile Dermatomyositis	Increased CXCR5 and function Mainly TFH with Th17 and Th2-like profile	[1]
ATD	Increased CXCR5, IL-21 high	[51]
Multiple Sclerosis	Increased CXCR5 IL-21 and IL-21R in neurons	[52,53]
Sjögren’s syndrome	Increased CXCR5 TFH with Th17 and Th2-like profile IL-17?	[54,55]

T_FH: Follicular helper T lymphocytes; SLE: Systemic lupus erythematosus; RA: Rheumatoid arthritis; ATD: Autoimmune thyroid disease; CXCR5: Chemokine (C-X-C motif) receptor 5; IL: Interleukin; Th: T helper.