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Lymphoid Tissue Inducer Cells: Pivotal Cells in the Evolution of CD4 Immunity and Tolerance?

By Peter J. L. Lane, Fabrina M. Gaspal, Fiona M. McConnell, David R. Withers and Graham Anderson

Abstract

Phylogeny suggests that the evolution of placentation in mammals was accompanied by substantial changes in the mammalian immune system: in particular lymph nodes and CD4 high affinity memory antibody responses co-evolved during the same period. Lymphoid tissue inducer cells (LTi) are members of an emerging family of innate lymphoid cells (ILCs) that are crucial for lymph node development, but our studies have indicated that they also play a pivotal role in the long-term maintenance of memory CD4 T cells in adult mammals through their expression of the tumor necrosis family members, OX40- and CD30-ligands. Additionally, our studies have shown that these two molecules are also key operators in CD4 effector function, as their absence obviates the need for the FoxP3 dependent regulatory T (Tregs) cells that prevent CD4 driven autoimmune responses. In this perspective article, we summarize findings from our group over the last 10 years, and focus specifically on the role of LTi in thymus. We suggest that like memory CD4 T cells, LTi also play a role in the selection and maintenance of the Tregs that under normal circumstances are absolutely required to regulate CD4 effector cells

Topics: Immunology
Publisher: Frontiers Research Foundation
OAI identifier: oai:pubmedcentral.nih.gov:3342352
Provided by: PubMed Central
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    Citations

    1. Abrogation of CD30 and OX40 signalspreventsautoimmunediseasein FoxP3 deficient mice.
    2. and Withers,D.R.(2012).Lymphoidtissue inducer cells: innate cells critical forCD4memoryresponses?Ann.N.
    3. (2008). Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularity.
    4. (2011). CD117(+) CD3(−) CD56(−)OX40L(high)cellsexpress IL-22 and display an LTi phenotype in human secondary lymphoid tissues.
    5. (2005). CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2.
    6. (1999). CD4 T cell traffic control: in vivo evidence thatligationof OX40onCD4Tcells by OX40-ligand expressed on dendriticcellsleadstotheaccumulation of CD4 T cells in B follicles.
    7. (2003). cellscostimulateprimedCD4Tcells through OX40 and CD30 at sites whereTcellscollaboratewithBcells.
    8. (1999). Cloning of the APECED gene provides new insight into human autoimmunity.
    9. (1999). Compromised OX40 function in CD28-deficient miceislinkedwithfailuretodevelop CXC chemokine receptor 5-positive CD4 cells and germinal centers.
    10. (2011). Control of central and peripheral tolerance by Aire.
    11. (2009). Ctla-4 controls regulatory T cell peripheral homeostasis and is required for suppression of pancreatic islet autoimmunity.
    12. (2010). Different routes of bacterial infection inducelong-livedTH1memorycells and short-lived TH17 cells.
    13. (2007). Early diversification of the TNF superfamily in teleosts: genomic characterization and expressionanalysis.J.Immunol.178,
    14. (1997). Expression and function of OX40 ligand on human dendritic cells.
    15. (2007). Fibroblastic reticular cells in lymphnodesregulatethehomeostasis of naive T cells.
    16. (2008). FibroblasticreticularcellsguideTlymphocyte entry into and migration within the splenic T cell zone.
    17. (2003). Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.
    18. (2008). Genome analysis of the platypus reveals unique signatures of evolution.
    19. (2008). Homeostasis of naive and memory T cells.
    20. (2004). IL-22 increases the innate immunity of tissues.
    21. (2008). IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia.
    22. (2009). IL7-hCD25 and IL7-Cre BAC transgenic mouse lines: new tools for analysis of IL-7
    23. (2009). Intraclonal competition limits the fate determination of regulatory T cells in the thymus.
    24. (2012). Lymphoid tissue inducer cells: pivotal cells in the evolution of CD4 immunity and tolerance?
    25. (2009). Lymphoid tissue inducerlike cells are an innate source of IL-17 and IL-22.
    26. (2003). Lymphotoxin pathway directs thymic Aire expression.
    27. (2010). Lymphotoxinsignalsfrompositively selected thymocytes regulate the terminal differentiation of medullary thymic epithelial cells.
    28. (2008). Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosalimmunedefense.Immunity 29,
    29. (1997). Molecular evolution of two vertebrate aryl hydrocarbon (dioxin) receptors (AHR1andAHR2)andthePASfamily.
    30. (2009). Neonatal tolerance revisited: a perinatal window for Aire control of autoimmunity.
    31. (1999). OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis.
    32. (2005). Opinion: inducible lymphoid tissues in the adult gut: recapitulation of a fetal developmentalpathway?Nat.Rev.Immunol.
    33. (2003). Organogenesis of lymphoid tissues.
    34. (2002). Origin of regulatory T cells with known specificity for antigen.
    35. (2005). OX40 signals during priming on dendritic cells Inhibit CD4 T cell proliferation: IL-4 switches off OX40 signals enabling rapid proliferation of Th2 effectors.
    36. (2007). OX40-mediated differentiation to effector function requires IL2 receptor signaling but not CD28, CD40, IL-12Rbeta2, or T-bet.
    37. (2011). paper pending published: 28
    38. (2007). RANK signals from CD4(+)3(−) inducer cells regulate development of Aireexpressing epithelial cells in the thymic medulla.
    39. (2008). Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulinAgenerationinthegut.Immunity 29,
    40. (2007). Selection of Foxp3+regulatoryTcellsspecific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells.
    41. (2010). Shared dependence on the DNA-binding factor TOX for the development of lymphoid tissue-inducer cell and NK cell lineages.
    42. (2011). T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse.
    43. (2008). The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity toenvironmentaltoxins.Nature 453,
    44. (2008). The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator.
    45. (1994). The Ikaros geneisrequiredforthedevelopment of all lymphoid lineages.
    46. (2001). The immune dysregulation,polyendocrinopathy,enteropathy, X-linked syndrome (IPEX) is causedbymutationsof FOXP3.Nat.
    47. The lymphotoxin beta receptor controlsorganogenesisandaffinitymaturation in peripheral lymphoid tissues.
    48. (2009). The survival of memory CD4+ T cells within the gut lamina propria requires OX40 and CD30 signals.
    49. (2008). The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance.
    50. (2007). The zebrafish retinoid-related orphan receptor (ror) gene family. Gene Expr.
    51. This is an open-access article distributed underthetermsoftheCreativeCommons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
    52. (2003). Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTbetaR.
    53. (2005). TNF/TNFR family members in costimulation of T cell responses.
    54. (2011). Transendocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.
    55. (2005). Two sides of a cellular coin: CD4+CD3− cells orchestrate memory antibody responses and lymph node organisation.
    56. (2001). Visualizing the generation of memory CD4 T cells in the whole body.
    57. (2012). Volume 3 | Article 24 | 5Lane et al. LTi in adaptive immunity
    58. (2012). Volume 3 | Article 24 | 6Lane et al. LTi in adaptive immunity
    59. (2001). X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy.

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