In the attempt to understand the origin of autoantibody (AAb) production
in patients with and at-risk for T1D, multiple studies have analyzed and
reported alterations in follicular helper T cells (Tfh) in presymptomatic
AAb-positive subjects and patients with T1D. Yet, it is still not clear whether
the regulatory counterpart of Tfh cells, represented by follicular regulatory T
cells (Tfr), is similarly altered. To address this question, we performed
analyses in peripheral blood, spleen and pancreatic lymph nodes (PLN) of organ
donor subjects with T1D. Blood analyses were also performed in living
AAb-negative and -positive subjects. While negligible differences in the
frequency and phenotype of blood Tfr cells were observed between T1D,
AAb-negative and AAb-positive adult subjects, the frequency of Tfr cells was
significantly reduced in spleen and PLN of T1D as compared to non-diabetic
controls. Furthermore, adoptive transfer of Tfr cells delayed disease
development in a mouse model of T1D, a finding that could indicate that Tfr
cells play an important role in peripheral tolerance and regulation of
autoreactive Tfh cells. Together, our findings provide evidence of Tfr cell
alterations within disease-relevant tissues in patients with T1D suggesting a
role for Tfr cells in defective humoral tolerance and disease pathogenesis.
Roles of follicular helper and regulatory T cells in allergic diseases and allergen immunotherapy