Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Jun;33(6):297-305.
doi: 10.1016/j.it.2012.04.006. Epub 2012 May 21.

Tertiary lymphoid organs in infection and autoimmunity

Katrijn Neyt  1 , Frédéric Perros, Corine H GeurtsvanKessel, Hamida Hammad, Bart N Lambrecht
Affiliations
Review

Tertiary lymphoid organs in infection and autoimmunity

Katrijn Neyt et al. Trends Immunol. 2012 Jun.

Abstract

The lymph nodes (LNs) and spleen have an optimal structure that allows the interaction between T cells, B cells and antigen-presenting dendritic cells (DCs) on a matrix made up by stromal cells. Such a highly organized structure can also be formed in tertiary lymphoid organs (TLOs) at sites of infection or chronic immune stimulation. This review focuses on the molecular mechanisms of TLO formation and maintenance, the controversies surrounding the nature of the inducing events, and the functions of these structures in infection, transplantation and autoimmunity.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Development and structure of secondary lymphoid structures. (a) During SLO development, the earliest instructive signal is from a neuronal cell that induces the local fibroblasts to upregulate CXCL13 and thus attract LTi cells. These cells express LTβ and instruct the local fibroblasts to become LTo cells that start producing chemokines for B cells (CXCL13), T cells and DCs (CCL19 and CCL21). At the same time, the fibroblasts upregulate cell adhesion molecules to allow LTis and recruited T and B cells to stick together. Local angiogenic growth factors are also made to allow the development of high endothelial venules (HEV), as well as afferent and efferent lymph vessels. (b) As a result, a well-organized structure with a separate B cell (blue) and T cell zone (red) is formed. This allows cell–cell contact at the appropriate time; and entry and exit of lymphocytes and antigen via the HEVs and lymphatics.
Figure 2
Figure 2
Development and structure of tertiary lymphoid structures. (a) During chronic immune responses or transplant rejection, DCs continuously present antigens to T and B cells. Activated B cells express LTβ and can act as potent LTi-like cells, to induce an LTo phenotype in local myofibroblasts. Alternatively, chronic antigen presentation by DCs might also lead to induction of a Th17 cell response that can also induce TLOs through unclear mechanisms. Th17 cells are held in place via interactions with podoplanin. (b) As in SLOs, TLOs are divided into discrete B and T cell areas. Although, fully formed TLO structures often contain only a single T cell area and a larger B cell area, in which GC reactions can be seen. These also contain DCs and FDCs. At the periphery, an elaborate network of lymphatics (Lyve1+ and Prox1+) is commonly found but it is currently unknown if these are afferent or efferent lymphatics.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Turley S.J. The stromal and haematopoietic antigen-presenting cells that reside in secondary lymphoid organs. Nat. Rev. Immunol. 2010;10:813–825. - PubMed
    1. van de Pavert S.A., Mebius R.E. New insights into the development of lymphoid tissues. Nat. Rev. Immunol. 2010;10:664–674. - PubMed
    1. Roozendaal R., Mebius R.E. Stromal cell-immune cell interactions. Annu. Rev. Immunol. 2011;29:23–43. - PubMed
    1. Eberl G. An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells. Nat. Immunol. 2004;5:64–73. - PubMed
    1. Vondenhoff M.F. LTbetaR signaling induces cytokine expression and up-regulates lymphangiogenic factors in lymph node anlagen. J. Immunol. 2009;182:5439–5445. - PMC - PubMed

Publication types