Peripheral naïve T cells via the interaction with tolerogenic dendritic cells (tDC)
differentiate into peripheral T (pTreg) cells, acquiring
the higher TCR affinity and transcription factor Forkhead Box P3 (FoxP3+). They operate in the following ways:
(1) competition with proliferating lymphocytes for IL-2 by CD25+ molecule, a part of the IL-2 receptor;
(2) promotion of immunosuppressive cytokines: IL-10, TGF-β, and IL-35;
(3) inhibition of helper T cells and ILC2 cells;
(4) upregulation of apoptosis in antigen-presenting and effector cells; and
(5) promotion of expression of coinhibitory molecules: CTLA-4, PD-1, BTLA, and LAG-3.
Immunoregulatory FoxP3-T cells, such as type 1 regulatory T (Tr1)
cell and type 3 helper T (Th3) cell provide their
pro-tolerogenic action at mucosal sites irrespective of the FoxP3+pTregs.