Circulating CCR7+ICOS+ Memory T Follicular Helper Cells in Patients with Multiple Sclerosis

Abstract

ObjectiveThis study is aimed at examining the potential roles of circulating memory T follicular helper (Tfh) cells in patients with multiple sclerosis (MS).MethodsThe numbers of different subsets of circulating memory Tfh cells in 25 patients with relapsed MS before and after treatment as well as 14 healthy controls (HC) were examined by flow cytometry. The levels of plasma IL-21 in all patients and cerebrospinal fluid (CSF) IL-21 in some MS patients and controls with non-inflammatory neuronal diseases (NND) were measured by ELISA.ResultsIn comparison with that in the HC, the numbers of circulating CD3+CD4+CXCR5+CD45RA-, ICOS+, CCR7+ and CCR7+ICOS+ memory Tfh cells and the levels of plasma IL-21 significantly increased in MS patients, but significantly decreased in the patients with complete remission (CR). The levels of CSF IL-21 were significantly higher in the MS patients than that in the NND patients. The numbers of CCR7+ICOS+ memory Tfh cells were positively correlated with the EDSS scores, the levels of plasma and CSF IL-21, IgG, MBP-Ab or MOG-Ab.ConclusionsOur findings indicated that circulating memory Tfh cells, especially CCR7+ICOS+ memory Tfh cells, may be associated with the relapse of MS and may serve as a new therapeutic target.

Follicular Helper T Cells in Autoimmunity

“…Equal pathological patterns were observed in other autoimmune diseases such as juvenile dermatomyositis and Sjögren's syndrome [85]. Increased levels of memory TFH cells and plasma IL-21 were observed in patients with MS compared to healthy controls and patients with complete remission of the disease [86].…”

“…However, further studies are needed to dissect the disease relevance of these novel T cellrelated candidate biomarkers and to precisely characterize murine and human TFH cells to understand the molecular mechanism that regulates their differentiation and functions. Thereby, targeting TFH cells to generate a longlasting protective antibody response by novel, functional vaccines might be possible in close future [86]. 2 Role and function of TFH cells in immunodeficiency, immune homeostasis, and autoimmunity and levels of potential biomarkers.…”

Circulating immune cells in multiple sclerosis

“…Such questions would be best addressed through thorough, multi-subset, longitudinal analysis from the earliest presentation of demyelinating disease. [16] " ("" in active disease) CD146 1 (% CD4) [30] No significant differences reported in the cited literature $ Tfh (% CD4) # Tfr (% T reg ) [52] # EM/RA (% PBMC) [56] $ Tc17 (% CD8) [72] $ FoxP3 1 (% CD8) [61] # CD27 1 (% B cells) in active disease [80] RRMS " Th17 (% CD4) [17] $ Th17 (% memory CD4) [6,18] " CD146 1 (% CD4) [30] " GM-CSF 1 (% CD4) [20] # CD39 1 (% T reg ) [44] # CD39 1 (% PBMC) [45] # memory T reg (% CD4) [35] # FoxP3 MFI [39,40] $ Tfh (% CD4) [52] " Tfh (number) [55] " ICOS 1 (% Tfh) [7] # Tfh1 (% Tfh) [7] # Tfr (% T reg ) [52] " Tfr17 (% T reg ) [52] # EM/RA (% PBMC) [56] " Tc17/IFN-g 1 Tc17 (% CD8) [70] " MAIT (% CD8) [65] # MAIT (% memory CD8 [67] and abT cells [66]) " GM-CSF 1 (% CD8) [20] $ B cells (% PBMC) [80] $ core subsets (% B cells) [80,81] # IL-10 1 (% B cells) [77] RRMS -active "" Th17 and Th17.1 (% memory CD4) [6,18] "" CD146 1 (% CD4) [30] # CD39 1 (% T reg ) [44] # memory T reg (% CD4) [35] # FoxP3 MFI [39,40] "" number of…”

High frequency of circulating follicular helper T cells is correlated with B cell subtypes in patients with ankylosing spondylitis

“…However, to the best of our knowledge, there have been only two studies regarding a novel, distinct subgroup of cluster of differentiation (CD)4 + T cells, known as follicular helper T cells (Tfh), in patients with AS (5,6). A number of previous studies have demonstrated that aberrant expression of circulating (c)Tfhs may mediate the development of autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis and Sjogren's syndrome (7)(8)(9)(10). Tfhs are known as specialized providers of help to B cells and persistently express C-X-C chemokine receptor type 5 (CXCR5), which drives Tfh migration into B cell follicles in response to the specific ligand CXCL13, which is expressed by follicular dendritic cells (11).…”