Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion

The darker side of follicular helper T cells: from autoimmunity to immunodeficiency

“…The alteration of T FHC cells has been reported in patients with various autoimmune diseases, such as rheumatoid arthritis, primary Sjogren's syndrome, juvenile dermatomyositis and autoimmune thyroid diseases, where T FHC cells are present at a higher frequency and show positive correlation with serum autoantibody titer in the patients. [52][53][54][55] Overall, these observations suggest an important role for T FHC cells in human autoimmunity. However, it should be noted that although T FHC cells resemble T FH cells in terms of ICOS and PD-1 expression, T FHC cells in SLE patients do not express Bcl6 and IL-21 that are hallmarks of classic T FH cells.…”

“…Furthermore, T FHC cells showed expression of ICOS and PD-1 but not Bcl6, similar to T FHC cells in lupus patients. 52 Evidence from other recent studies also points toward a relationship between T FHC and T FH cells. The patients deficient in ICOS and CD40L lack T FHC cells, whereas T FHC cells expressing ICOS are overrepresented in SLE and rheumatoid arthritis patients.…”

“…50 Recent studies have further provided clearer evidence on the role of T FH cells in promotion of both systemic and organ-specific autoimmune diseases in humans. [51][52][53][54][55] Simpson et al 51 performed an elegant study investigating the role of T FH cells in patients with SLE and Sjogren's syndrome. They found an overrepresented population of CD4 1 CXCR5 1 T FH cell-like cells in the blood, referred to as circulating T FH (T FHC ) cells, of a subset of the SLE patients (14 out of 46), which expressed ICOS and PD-1 compared with healthy controls.…”

“…This is in accordance with the fact that T FH cells may downregulate Bcl6 over weeks after antigenic challenge. 56 Recently, Morita et al 52 shed light on the relationship between T FHC (CD4 1 CXCR5 1 ) and T FH cells and convincingly demonstrated that T FHC cells share functional, and to some extent phenotypic, properties of T FH cells present in the lymphoid organs of humans and mice, and constitute a subset of circulating pool of memory T FH cells. They found T FHC cells to be potent at providing help for B-cell responses, such as production of plasmablasts and promotion of class switching through IL-21.…”

Role of interleukin-21 in HBV infection: friend or foe?

“…26 Several studies have demonstrated that CXCR5 1 CD4 1 T cells in the peripheral circulation shared some properties with Tfh cells. [40][41][42] Moreover, CXCR5 1 CD4 1 T cells derived from both the circulation and germinal centers potently induced antibody production in in vitro cocultures with autologous B cells. 42,43 Thus, circulating CXCR5 1 CD4 1 T cells, which are easily accessible in the peripheral blood, may serve as surrogates for assessing the function of Tfh cells.…”