Its main purpose is to ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease.
[1] Peripheral tolerance can also serve a purpose in preventing an immune response to harmless food antigens and allergens.
[5][4] Tregs, which are also generated during thymic T cell development, further suppress the effector functions of conventional lymphocytes in the periphery.
Tregs are the central mediators of immune suppression and they play a key role in maintaining peripheral tolerance.
TCR of nTregs shows a high affinity for self-peptides, Induced Tregs (iTreg) develop from conventional naive helper T cells after antigen recognition in presence of TGF-β and IL-2.
iTregs are enriched in the gut to establish tolerance to commensal microbiota and harmless food antigens.
These include depletion of IL-2 from the environment, secretion of anti-inflammatory cytokines IL-10, TGF-β and IL-35[11] and induction of apoptosis of effector cells.
CTLA-4 is a surface molecule present on Tregs which can prevent CD28 mediated costimulation of T cells after TCR antigen recognition.
After encountering an antigen with recognition danger or pathogen-associated molecular patterns, DCs start the secretion of proinflammatory cytokines, express costimulatory molecules CD80 and CD86 and migrate to the lymph nodes to activate naive T cells.
The immunogenic potential of iDCs is weak, because of the low expression of costimulatory molecules and a modest level of MHCII.
iDCs perform endocytosis and phagocytosis of foreign antigens and apoptotic cells, which occurs physiologically in peripheral tissues.
Antigen-loaded iDCs migrate to the lymph nodes, secrete IL-10, TGF-β and present antigen to the naive T cells without costimulation.
[13] Tolerogenic DCs express FasL and TRAIL to directly induce apoptosis of responding T cells.
In mesenteric lymph nodes(mLN), LNSCs can induce Tregs directly by secretion of TGF-β or indirectly by imprinting mLN-resident DCs.
[21] After antigen exposure and costimulation, naive T cells start the process called quiescence exit, which results in proliferation and effector differentiation.
[23] As cells exit a quiescent state they will up regulate enzymes that are responsible for production of essential pathways (nucleic acids, proteins, carbohydrates, etc.).
In the absence of costimulation, there is no MAPK signaling in T cells and translocation of transcription factor AP-1 into the nucleus is impaired.
This disbalance of transcription factors in T cells results in the expression of several genes involved in forming an anergic state.
These areas are protected by several mechanisms: Fas-ligand expression binds Fas on lymphocytes inducing apoptosis, anti-inflammatory cytokines (including TGF-beta and interleukin 10) and blood-tissue-barrier with tight junctions between endothelial cells.