Anatomy of tolerance

Abstract

Further probing as to how lymph node stromal cells and fibers interact with and determine the character of immune responses should yield fundamental insights into tolerance and immunity. Manipulation of lymph node structure and associated unique cell types and molecules may allow therapeutic interventions in the tolerogenic process.

The lymph node stromal laminin α5 shapes alloimmunity

“…The CR contains a higher concentration of FRCs and is a site for T cell and DC interactions crucial for tolerance induction and maintenance (53). Th17 cells and Tregs are primed in the CR and the choice between immunity and tolerance may depend on other local factors, such as stromal laminin signals, as shown here (54). Induction of adaptive iTregs occurred preferentially in the CR compared with spleen ( Figure 7C), consistent with the earlier report showing that iTreg induction occurs preferentially in LNs (55).…”

Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival

“…LNs are extremely compartmentalized secondary lymphoid organs that provide an optimal environment for freshly recruited lymphocytes to interact with antigen-presenting cells. The LN is a critical site for the priming and activation of alloreactive T cells, but it also plays an important role in the manipulation of the immune response toward regulation and tolerance (2,(5)(6)(7). The latter is highlighted by studies that detail the importance of the LN in promoting the activity of regulatory T cells (Tregs) (8,9).…”

IL-10 from marginal zone precursor B cells controls the differentiation of Th17, Tfh and Tfr cells in transplantation tolerance

“…These fibers and networks not only help in the migration of T cells, B cells and APCs; but also provide a platform for cognate interactions which play important roles in shaping immunity and tolerance [49]. Reagents that disrupt the stromal fiber network prevent the generation and maintenance of transplantation tolerance [50,51].…”