Abstract
T cell-mediated immune tolerance is a state of unresponsiveness of T cells towards specific self or non-self antigens. This is particularly essential during prenatal/neonatal period when T cells are exposed to dramatically changing environment and required to avoid rejection of maternal antigens, limit autoimmune responses, tolerate inert environmental and food antigens and antigens from non-harmful commensal microorganisms, promote maturation of mucosal barrier function, yet mount an appropriate response to pathogenic microorganisms. The cell-intrinsic and cell extrinsic mechanisms promote the generation of prenatal/neonatal T cells with distinct features to meet the complex and dynamic need of tolerance during this period. Reduced exposure or impaired tolerance in early life may have significant impact on allergic or autoimmune diseases in adult life. The uniqueness of conventional and regulatory T cells in human umbilical cord blood (UCB) may also provide certain advantages in UCB transplantation for hematological disorders.
Highlights
Immune tolerance is a state of unresponsiveness of the immune cells towards specific self or non-self antigens
Having different dynamics in T cell emergence, the origin of human and murine prenatal/perinatal T cells with distinct intrinsic properties, including short T cell receptor (TCR), promiscuous antigen recognition, and high CD5 expression, is the same, i.e. both are derived from hematopoietic stem cells (HSCs) from fetal liver [53, 58, 105,106,107,108]
The detailed in vivo experiments in murine system further demonstrate that ectopic expression of Lin28b or loss of Ezh2 in adult bone marrow (BM) hematopoietic stem/progenitor cells (HSPCs) induces activation of fetal-specific genes in HSPCs and fetal-like lymphopoiesis, including the development of B-1 cells, marginal zone B cells, and gd T cells [106, 109]
Summary
Immune tolerance is a state of unresponsiveness of the immune cells towards specific self or non-self antigens. The high affinity between TCRs and self-peptide/MHC complexes did not increase the likelihood to generate autoreactive T cells during neonatal period or incidence of autoimmune pathologies [36,37,38], at least in a rodent model with the transplantation of NOD thymi to NOD.scid mice [39]. Instead, it promotes Tregs’ capability to undergo proliferation and likely, to modulate specific immune responses [40, 41]. Together with delayed TdT expression and similar TCR sequencing feature between human fetal T cells and mouse neonatal T cells, it is believed, more evidence is needed, that human TCR repertoire has high cross-reactivity
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