Follicular Helper T Cells in Systemic Lupus Erythematosus: Why Should They Be Considered as Interesting Therapeutic Targets?

Table 1

Function of -related molecules during differentiation.

T cell molecule	Ligand	Function in mice	Function in humans
CD28	CD80/86	CD28^−/− mice fail to form GC [10]	ND
CD40L	CD40	T cell accumulation in B cell follicles relies on CD40-dependent maturation of DC [11]	ND
OX40	OX40L	T cells do not migrate to B cell follicles in immunized OX40^−/− mice [11]; OX40L instructs CD4^+ T cells to express CXCR5 [130]; CD28^−/− T cells fail to upregulate OX40 [10]; OX40-OX40L interaction allows CD4^+ T cells to accumulate in B cell follicles [131]	OX40 signal promotes CD4^+ T cells to express T molecules and to become functional B cell helpers [84]
ICOS	ICOSL	ICOS provides a critical early signal to induce Bcl6 [12]; Generation of T depends on the PI3K signaling initiated by ICOS [132]	LOF mutations in ICOS reduce cT frequencies [133]
IL6R	IL-6	IL-6 promotes the differentiation of naive T cells in helper B cells [14]; IL-6^−/− mice harbor reduced Bcl6 expression and T differentiation [134]	Plasmablasts-derived IL-6 induces T differentiation [17]
IL-12R	IL-12	ND	IL-12 induces CD4^+ T cells to become IL-21-producing T-like cells [15]; IL-12 induces naive CD4^+ T cells to acquire T characteristics and the ability to provide B cell help [16]
IL-21R	IL-21	T cells activated by IL-21 acquire T gene expression and function [18]; IL-21^−/− mice have reduced T differentiation and GC formation [134]	LOF mutations in IL-21R skewed T differentiation toward an IFNγ^+PD1^+ phenotype [133]

GC: germinal center; DC: dendritic cells; ND: not determined; LOF: loss of function; cT: circulating T; PC: plasma cells.