. 2015 Aug 2;2015:638968. doi: 10.1155/2015/638968

Table 1.

TFH cells and TFH-associated molecules in neuroautoimmune diseases and their animal models.

Neuroautoimmune diseases	Changes of TFH cells and TFH-associated molecules	Relevance to the diseases	References
MS	↑ frequency of circulating CD4⁺CXCR5⁺ICOS⁺ T cells in RRMS and SPMS patients ↑ gene expression of ICOS, IL-21, and IL-21R in purified CD4⁺ T cells in SPMS patients ↑ ICOS expression in CSF cells in progressive MS patients ↑ IL-21 expression of CD4⁺ T cells in infiltrating active lesions of CNS ↓ frequency of blood CXCR3⁺ Th1-like TFH cells in MS patients ↑frequency of blood CCR6⁺ Th17-like TFH cells in PPMS patients	Positive correlation between circulating CD4⁺CXCR5⁺ICOS⁺ T cells and disease progression in SPMS	[64–66]

EAE	CXCR5 mRNA present in spinal cords CNS infiltrating CXCR5⁺ cells were CD3⁺CD4⁺ T cells in spinal cord MNCs		[70]

NMO/NMOSD	↑ frequency of circulating CD4⁺CXCR5⁺PD-1⁺ T cells ↑ serum level of IL-21 ↑ secretion of IL-21 in PBMC cultures ↑ serum and CSF levels of CXCR5	A correlation between circulating CD4⁺CXCR5⁺PD-1⁺ T cells and disease activity Positive correlation between the level of IL-21 produced by peripheral blood CD4⁺ T cells and EDSS score Positive correlation between CSF CXCL13 level and disease disability	[83–85]

MG	↑ frequency of circulating CD4⁺CXCR5⁺ T cells, CD4⁺CXCR5⁺CD45RO⁺ T cells, CD4⁺CXCR5⁺ PD-1^hi T cells, and CD4⁺CXCR5⁺ICOS^hi T cells ↑ serum level of CXCL13 ↑ expression of IL-21 mRNA in PBMCs	Positive correlation between circulating CD4⁺CXCR5⁺ T cells and disease severity Positive correlation between circulating CD4⁺CXCR5⁺ICOS^hi T cells and serum anti-AChR Ab concentration Positive correlation between circulating CD4⁺CXCR5⁺PD-1^hi T cells and serum anti-AChR Ab concentration Positive correlation between serum level of CXCL13 and disease severity Positive correlation between serum level of CXCL13 or expression of IL-21 mRNA in PBMCs and circulating CD4⁺CXCR5⁺ICOS^hi T cells	[97–100]

EAMG	↑ frequency of CD4⁺CXCR5⁺PD-1⁺ TFH cells and increased expression of Bcl-6 and IL-21 in spleens	Positive correlation between serum level of anti-AChR Abs and the frequency of TFH cells in spleen	[102]

AChR, acetylcholine receptor; Bcl-6, B cell lymphoma 6; CCR6, CC chemokine receptor 6; CNS, central nervous system; CSF, cerebrospinal fluid; CXCL13, CXC-chemokine ligand 13; CXCR3, CXC-chemokine receptor 3; CXCR5, CXC-chemokine receptor 5; EAE, experimental autoimmune encephalomyelitis; EAMG, experimental autoimmune myasthenia gravis; EDSS, expanded disability status scale; ICOS, inducible costimulator; IL-21, interleukin 21; IL-21R, IL-21 receptor; MG, myasthenia gravis; MNCs, mononuclear cells; MS, multiple sclerosis; NMO, neuromyelitis optica; NMOSD, neuromyelitis optica spectrum disorders; PBMC, peripheral blood mononuclear cell; PD-1, programmed death-1; RRMS, relapsing remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.