Summary
Follicular T helper (Tfh) and regulatory (Tfreg) cells are distinct
subsets of CD4+T lymphocytes, regulating humoral
immune responses in the germinal center. Dysregulated Tfh and Tfreg
cells are believed to associate with autoimmunity. Here, we evaluated
the frequencies of circulating
CXCR5+PD-1+ Tfh (cTfh) and
CXCR5+PD-1+FoxP3+CD25+Tfreg (cTfreg) cells, and their corresponding cytokines from the
peripheral blood mononuclear cells of 20 patients with
relapsing-remitting multiple sclerosis (MS) and 12 age- and sex-matched
healthy controls (HC). Subsets of cTfh cells by Th1 and Th17 related
surface markers (CXCR3 and CCR6) were also evaluated. We found the
frequency of cTfh cells was significantly higher in MS patients compared
to HC (p=0.002). Conversely, cTfreg cells were downregulated in MS
patients (p<0.0001). IL-21 producing cTfh cells were
significantly increased in MS patients (p=0.003), while IL-10 secreting
cTfreg cells were decreased in MS compared to HC (p=0.02). Among cTfh
cells, cTfh17.1 cells were major subtypes that were significantly
increased in MS compared to HC (p=0.002) and the frequency of IL-21
secreting cells were highest. These results suggest that an imbalanced
distribution of cTfh and cTfreg exist in MS, which contributes to
reciprocally altered IL-21 and IL-10 production.
Keywords: Multiple sclerosis, Follicular T helper cells,
Follicular regulatory T cells.