Advertisement

Synthesis of Functional Tertiary Lymphoid Organs

  • Yuka Kobayashi
  • Koichi Kato
  • Makoto Nakamura
  • Takeshi Watanabe
Chapter

Abstract

The regeneration of functional immune organ will be one of major focus in future immunology research. It will be an useful tool which induces efficient immune responses in the body on demand and offers effective ways to restore the immune status and treat uncontrollable obstinate diseases such as cancer, autoimmune diseases, severe infection and immuno-insufficiency/deficiency caused by tissue damages, abnormality, primary defect and aging. Artificially synthesized lymphoid organs may also provide us with a highly informative method not only for clinical aim but also basic study on the development and functions of immunological tissues and organs. We first reported successful generation of artificially-constructed lymph node-like tertiary lymphoid tissues at ectopic sites in mouse by applying certain stromal cell lines (Suematsu S, Watanabe T. Nat Biotechnol 22(12):1539–1545, 2004; Okamoto N et al. J Clin Invest 117(4):997–1007, 2007; Kobayashi Y, Watanabe T. Trends Immunol 31(11):422–428, 2010). They showed a remarkable ability to induce immune responses upon antigen stimulation, especially when transplanted into naïve or immune-compromised hosts. In this review, we discuss about the rationale and method for the synthesis of functional tertiary lymph node-like lymphoid tissues in mouse. Especially, we discuss here on the method with applying only soluble factors but without using any stromal cell, that enables proper accumulation and functional organization of immune cells in grafts.

Keywords

Stromal Cell Lymphoid Tissue Mesenchymal Stromal Cell Collagen Sponge Follicular Dendritic Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations

SLO

secondary lymphoid organs

TLO

tertiary lymphoid organs

LN

lymph node

PP

Payer’s patches

DC

dendritic cells

FDC

follicular dendritic cells

FRC

fibroblastic reticular cells

HEV

high endothelial venules

RIP- LTα

rat insulin promotor expressing Lta (lymphotoxin-α) gene

LTi

lymphoid tissue inducer

LTo

lymphoid tissue organizer

LTRβ

lymphotoxin receptor-beta

RA

retinoic acid

VEGFc

vessel endothelial growth factor

Aire

autoimmune regulator

MDSCs

myeloid-derived suppressor cells

Treg cells

regulatory T cells

HSPGs

heparan sulfate proteoglycans

HS

heparan sulfate

TES

tissue-engineered spleen

GC

germinal center

aAPC

artificial antigen-presenting cells

aLN

artificial lymph nodes

iPS

induced pluripotent stem cells

Notes

Acknowledgements

This work was supported by the Grant-in-Aid for Scientific Research on Priority Areas from MEXT, Japan (Grant No. 24111009)

Disclosure

Authors report no conflicts of interest.

References

  1. Aberle T, Franke K, Rist E et al (2014) Cell-type specific four-component hydrogel. PLoS One 9(1):e86740PubMedPubMedCentralCrossRefGoogle Scholar
  2. Akita M, Murata E, Merker HJ et al (1997) Morphology of capillary-like structures in a three-dimensional aorta/collagen gel culture. Ann Anat 179(2):127–136PubMedCrossRefGoogle Scholar
  3. Aloisi F, Pujol-Borrell R (2006) Lymphoid neogenesis in chronic inflammatorydiseases. Nat Rev Immunol 6(3):205–217PubMedCrossRefGoogle Scholar
  4. Ansel KM, Ngo VN, Hyman PL et al (2000) A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 406(6793):309–314PubMedCrossRefGoogle Scholar
  5. Bai Z, Hayasaka H, Kobayashi M et al (2000) CXC chemokine ligand 12 promotes CCR7-dependent naive T cell trafficking to lymph nodes and Peyer’s patches. J Immunol 182(3):1287–1295CrossRefGoogle Scholar
  6. Benezech C, White A, Mader E et al (2010) Ontogeny of stromal organizer cells during lymph node developmennt. J Immunol 184:4521–4530PubMedPubMedCentralCrossRefGoogle Scholar
  7. Benezech C, Mader E, Desanti G et al (2012) Lymphotoxin-β receptor signaling through NF-κB2-RelB pathway reprogams adipocyte precursors as lymph node stromal cells. Immunity 37:1–14CrossRefGoogle Scholar
  8. Benezech C, Nayar S, Finney BA et al (2014) CLEC-2 is required for development and maintenance of lymph nodes. Blood 123(20):3200–3206PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bertozzi CC, Schmater AA, Mericko P et al (2010) Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling. Blood 116(4):661–670PubMedPubMedCentralCrossRefGoogle Scholar
  10. Buettner M, Pabst R, Bode U (2010) Stromal cell heterogeneity in lymphoid organs. Trends Immunol 31(2):80–86PubMedCrossRefGoogle Scholar
  11. Butler MO, Lee JS, Ansen S et al (2007) Long-lived antitumor CD8+ lymphocytes for adoptive therapy generated using an artificial antigen-presenting cell. Clin Cancer Res 13(6):1857–1867PubMedCrossRefGoogle Scholar
  12. Chai Q, Onder L, Scandella E et al (2013) Maturation of lymph node fibroblastic reticular cells from myofibroblastic precuosors is critical for antiviral immunity. Immunity 38:1–12CrossRefGoogle Scholar
  13. Chen RR, Silva EA, Yuen WW et al (2007) Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation. Pharm Res 24(2):258–264PubMedCrossRefGoogle Scholar
  14. Chyou S, Ekland EH, Carpenter AC (2008) Fibroblast-type reticular stromal cells regulate the lymph node vasculature. J Immunol 181(6):3887–3896PubMedPubMedCentralCrossRefGoogle Scholar
  15. Cohen JN, Guidi CJ, Tewalt EF et al (2010) Lymph node-resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation. J Exp Med 207(4):681–688PubMedPubMedCentralCrossRefGoogle Scholar
  16. Cremasco V, Woodruff MC, Onder L et al (2014) B cell homeostasis and follicle confines are governed by fibroblastic reticular cells. Nat Immunol 15:973–981PubMedPubMedCentralCrossRefGoogle Scholar
  17. Cupedo T, Crellin NK, Papazian N et al (2009) Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nat Immunol 10(1):66–74PubMedCrossRefGoogle Scholar
  18. Cupedo T, Stroock A, Coles M et al (2012) Application of tissue engineering to the immune system: development of artificial lymph nodes. Front Immunol 3:343. doi: 10.3389/fimmu.2012.00343 PubMedPubMedCentralCrossRefGoogle Scholar
  19. Danner R, Chaudhari SN, Rosenberger J et al (2011) Expression of HLA class II molecules in humanized NOD.Rag1KO.IL2RγcKO mice is critical for development and function of human T and B cells. PLoS One 6(5):e19826. doi: 10.1371/journal.pone.0019826 PubMedPubMedCentralCrossRefGoogle Scholar
  20. Dejardin E, Droin NM, Delhase M et al (2002) The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity 17(4):525–535PubMedCrossRefGoogle Scholar
  21. Dieu-Nosjean M-C, Goc J, Giraldo NA et al (2014) Tertiary lymphoid structures in cancer and beyond. Trends Immunol 35(11):571–580PubMedCrossRefGoogle Scholar
  22. Drayton DL, Ying X, Lee J (2003) Ectopic LT alpha beta directs lymphoid organ neogenesis with concomitant expression of peripheral node addressin and a HEV-restricted sulfotransferase. J Exp Med 197(9):1153–1163PubMedPubMedCentralCrossRefGoogle Scholar
  23. Drayton DL, Liao S, Mounzer RH, Ruddle NH (2006) Lymphoid organ development: from ontogeny to neogenesis. Nat Immunol 7(4):344–353PubMedCrossRefGoogle Scholar
  24. Eberl G, Marmon S, Sunshine MJ et al (2004) An essential function for the nuclear receptor RORγ (t) in the generation of fetal lymphoid tissue inducer cells. Nat Immunol 5(1):64–73PubMedCrossRefGoogle Scholar
  25. Evans I, Kim MY (2009) Involvement of lymphoid inducer cells in the development of secondary and tertiary lymphoid structure. BMB Rep 42(4):189–193PubMedCrossRefGoogle Scholar
  26. Fan L, Reilly CR, Luo Y et al (2000) Cutting edge: ectopic expression of the chemokine TCA4/SLC is sufficient to trigger lymphoid neogenesis. J Immunol 164(8):3955–3959PubMedCrossRefGoogle Scholar
  27. Flavell RA, Sanjabi S, Wrzesinski SH et al (2010) The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol 10(8):554–567PubMedCrossRefGoogle Scholar
  28. Fletcher AL, Lukacs-Kornek V, Reynoso ED et al (2010) Lymph node fibroblastic reticular cells directly present peripheral tissue antigen under steady-state and inflammatory conditions. J Exp Med 207(4):689–697PubMedPubMedCentralCrossRefGoogle Scholar
  29. Fletcher AL, Malhotra D, Acton SE et al (2011) Reproducible isolation of lymph node stromal cells reveals site- dependent differences in fibroblastic reticular cells. Front Immunol. doi: 10.3389/fimmu.2011.00035
  30. Fu Y, Chaplin D (1999) Development and maturation of secondary lymphoid tissues. Annu Rev Immunol 17:399–433PubMedCrossRefGoogle Scholar
  31. Fukuyama S, Nagatake T, Kim DY et al (2006) Cutting edge: uniqueness of lymphoid chemokine requirement for the initiation and maturation of nasopharynx-associated lymphoid tissue organogenesis. J Immunol 177(7):4276–4280PubMedCrossRefGoogle Scholar
  32. Geurtsvankessel CH, Willart MA, Bergen IM et al (2009) Dendritic cells are crucial for maintenance of tertiary lymphoid structures in the lung of influenza virus-infected mice. J Exp Med 206(11):2339–2349PubMedPubMedCentralCrossRefGoogle Scholar
  33. Giese C, Demmler CD, Ammer R et al (2006) A human lymph node in vitro – challenges and progress. Artif Organs 30(10):803–808PubMedCrossRefGoogle Scholar
  34. Glanville SH, Bekiaris V, Jenkinson EJ et al (2009) Transplantation of embryonic spleen tissue reveals a role for adult non-lymphoid cells in initiating lymphoid tissue organization. Eur J Immunol 39(1):280–289PubMedPubMedCentralCrossRefGoogle Scholar
  35. Grabner R, Lotzer K, Dopping S et al (2009) Lymphotoxin beta receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE-/- mice. J Exp Med 206(1):233–248PubMedPubMedCentralCrossRefGoogle Scholar
  36. Griffith LG, Swartz MA (2006) Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol 7(3):211–224PubMedCrossRefGoogle Scholar
  37. Grikscheit TC, Sala FG, Ogilvie J et al (2008) Tissue-engineered spleen protects against overwhelming pneumococcal sepsis in a rodent model. J Surge Res 149(2):214–218CrossRefGoogle Scholar
  38. Hadamitzky C, Spohr H, Debertin AS et al (2010) Age-dependent histoarchitectural changes in human lymph nodes: an underestimated process with clinical relevance? J Anat 216(5):556–562PubMedPubMedCentralCrossRefGoogle Scholar
  39. Hammerschmidt SI, Ahrendt M, Bode U et al (2008) Stromal mesenteric lymph nodecells are essential for the generation of gut-homing T cells in vivo. J Exp Med 205(11):2483–2490PubMedPubMedCentralCrossRefGoogle Scholar
  40. Hjelmstrom P, Fjell J, Nakagawa T et al (2000) Lymphoid tissue homing chemokines are expressed in chronic inflammation. Am J Pathol 156(4):1133–1138PubMedPubMedCentralCrossRefGoogle Scholar
  41. Hori Y, Stern PJ, Hynes RO et al (2009) Engulfing tumors with synthetic extracellular matrices for cancer immunotherapy. Biomaterials 30(35):6757–6767PubMedPubMedCentralCrossRefGoogle Scholar
  42. Hu D, Mohanta SK, Yin C et al (2015) Artery teriary lymphoid organs control aorta immunity and protect against atherosclerosis via vascular smooth muscle cell lymphotoxin β receptors. Immunity 42:1100–1115PubMedPubMedCentralCrossRefGoogle Scholar
  43. Ishikawa F, Yasukawa M, Lyons B et al (2005) Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood 106(5):1565–1573PubMedPubMedCentralCrossRefGoogle Scholar
  44. Ito M, Hiramatsu H, Kobayashi K et al (2002) NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood 100(9):3175–3182PubMedCrossRefGoogle Scholar
  45. Iwata M, Hirakiyama A, Eshima Y et al (2004) Retinoic acid imprints gut-homing specificity on T cells. Immunity 21(4):527–538PubMedCrossRefGoogle Scholar
  46. Jaiswal S, Smith K, Ramirez A et al (2015) Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice. Exp Biol Med 240(1):67–78CrossRefGoogle Scholar
  47. Johnson Z, Proudfoot AE, Handel TM (2005) Interaction of chemokines and glycosaminoglycans: a new twist in the regulation of chemokine function with opportunities for therapeutic intervention. Cytokine Growth Factor Rev 16(6):625–636PubMedCrossRefGoogle Scholar
  48. Kalamajski S, Aspberg A, Oldberg A (2007) The decorin sequence SYIRIADTNIT binds collagen type I. J Biol Chem 282(22):16062–16067PubMedCrossRefGoogle Scholar
  49. Katakai T, Hara T, Lee JH et al (2004) A novel reticular stromal structure in lymph node cortex; an immuno-platform for interactions among dendritic cells, T cells and B cells. Int Immunol 16(8):1133–1142PubMedCrossRefGoogle Scholar
  50. Kawabuchi M, Nakamura K, Hirata K (1996) Morphological study of thymus stromal cells (TEL-2 cell) which play a role in the elimination of double positive immature thymocytes by phagocytosis. Anat Rec 244(3):271–283PubMedCrossRefGoogle Scholar
  51. Kim D, Mebius RE, Macmicking JD et al (2000) Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE. J Exp Med 192(10):1467–1478PubMedPubMedCentralCrossRefGoogle Scholar
  52. Kim MY, Mcconnell FM, Gaspal FM et al (2007) Function of CD4+CD3- cells in relation to B- and T-zone stroma in spleen. Blood 109(4):1602–1610PubMedCrossRefGoogle Scholar
  53. Kim MY, Kim KS, Mcconnell F, Lane P (2009) Lymphoid tissue inducer cells: architects of CD4 immune responses in mice and men. Clin Exp Immunol 157(1):20–26PubMedPubMedCentralCrossRefGoogle Scholar
  54. Kobayashi Y, Watanabe T (2010) Synthesis of artificial lymphoid tissue with immunological function. Trends Immunol 31(11):422–428PubMedCrossRefGoogle Scholar
  55. Kobayashi S, Miura H, Shibuya H et al (2013) A distinct human CD4+ T cell subset that secretes CXCL13 in rheumatoid synovitis. Arthritis Rheum 65:3063–3072PubMedCrossRefGoogle Scholar
  56. Krautler NJ, Kana V, Kranich J et al (2012) Follicular Dendritic Cells emerge from ubiquitous perivascular precursors. Cell 150:194–206PubMedPubMedCentralCrossRefGoogle Scholar
  57. Kuzin I, Sun H, Moshkani S et al (2011) Long-term immunologically competent human peripheral lymphoid tissue cultures in a 3D bioreactor. Biotechnol Bioeng 108:1430–1440PubMedPubMedCentralCrossRefGoogle Scholar
  58. Lane P, Kim M-Y, Withers D et al (2008) Lymphoid tissue inducer cells in adaptive CD4 T cell dependent responses. Semin Immunol 20:159–163PubMedCrossRefGoogle Scholar
  59. Legrand N, Ploss A, Balling R et al (2009) Humanized mice for modeling human infectious disease: challenges, progress, and outlook. Cell Host Microbe 6(1):5–9PubMedCrossRefGoogle Scholar
  60. Lotzer K, Dopping S, Connert S et al (2010) Mouse aorta smooth muscle cells differentiate into lymphoid tissue organizer-like cells on combined tumor necrosis factor receptor-1/lymphotoxin beta-receptor NF-kappaB signaling. Arterioscler Thromb Vasc Biol 30(3):395–402PubMedPubMedCentralCrossRefGoogle Scholar
  61. Luther SA, Bidgol A, Hargreaves DC et al (2002) Differing activities of homeostatic chemokines CCL19, CCL21, and CXCL12 in lymphocyte and dendritic cell recruitment and lymphoid neogenesis. J Immunol 169(1):424–433PubMedCrossRefGoogle Scholar
  62. Luther SA, Ansel KM, Cyster JG (2003) Overlapping roles of CXCL13, interleukin 7 receptor alpha, and CCR7 ligands in lymph node development. J Exp Med 197(9):1191–1198PubMedPubMedCentralCrossRefGoogle Scholar
  63. Lutolf MP, Hubbell JA (2005) Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat Biotechnol 23(1):47–55PubMedCrossRefGoogle Scholar
  64. Lutolf MP, Weber FE, Schmoekel HG et al (2003) Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat Biotechnol 21(5):513–518PubMedCrossRefGoogle Scholar
  65. Manzo A, Bugatti S, Caporali R et al (2007) CCL21 expression pattern of human secondary lymphoid organ stroma is conserved in inflammatory lesions with lymphoid neogenesis. Am J Pathol 171(5):1549–1562PubMedPubMedCentralCrossRefGoogle Scholar
  66. Mebius R (2007) Organogenesis of lymphoid tissues. Nat Rev Immunol 3(4):292–303CrossRefGoogle Scholar
  67. Meier D, Bornmann C, Chappaz S (2007) Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. Immunity 26(5):643–654PubMedCrossRefGoogle Scholar
  68. Molenaar R, Greuter M, Van Der Marel AP et al (2009) Lymph node stromal cells support dendritic cell-induced gut-homing of T cells. J Immunol 183(10):6395–6402PubMedCrossRefGoogle Scholar
  69. Mueller SN, Ahmed R (2008) Lymphoid stroma in the initiation and control of immune responses. Immunol Rev 224:284–294PubMedCrossRefGoogle Scholar
  70. Nakashima M, Mori K, Maeda K, Kishi H et al (1990) Selective elimination of double-positive immature thymocytes by a thymic epithelial cell line. Eur J Immunol 20(1):47–53PubMedCrossRefGoogle Scholar
  71. Nasr IW, Reel M, Oberbarnscheidt MH et al (2007) Tertiary lymphoid tissues generate effector and memory T cells that lead to allograft rejection. Am J Transplant 7(5):1071–1079PubMedCrossRefGoogle Scholar
  72. Neyt K, Perros F, GeurtsvanKessel CH et al (2012) Tertiary lymphoid organs in infection and autoimmunity. Trends Immunol 33(6):297–305PubMedCrossRefGoogle Scholar
  73. Niklason LE, Gao J, Abbott WM et al (1999) Functional arteries grown in vitro. Science 284(5413):489–493PubMedCrossRefGoogle Scholar
  74. Nojima T, Haniuda K, Moutai T et al (2011) In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo. Nat Commun. doi: 10.1038/ncomms1475
  75. Okamoto N, Chihara R, Shimizu C et al (2007) Artificial lymph nodes induce potent secondary immune responses in naive and immunodeficient mice. J Clin Invest 117(4):997–1007PubMedPubMedCentralCrossRefGoogle Scholar
  76. Pan WR, Suami H, Taylor GI (2008) Senile changes in human lymph nodes. Lymphat Res Biol 6(2):77–83PubMedCrossRefGoogle Scholar
  77. Peduto L, Dulauroy S, Lochner M et al (2009) Inflammation recapitulates the ontogeny of lymphoid stromal cells. J Immunol 182(9):5789–5799PubMedCrossRefGoogle Scholar
  78. Perez A, Grikscheit TC, Blumberg RS et al (2002) Tissue-engineered small intestine: ontogeny of the immune system. Transplantation 74(5):619–623PubMedCrossRefGoogle Scholar
  79. Randall TD, Carragher DM, Rangel-Moreno J (2008) Development of secondary lymphoid organs. Annu Rev Immunol 26:627–650PubMedPubMedCentralCrossRefGoogle Scholar
  80. Reif K, Ekland EH, Ohl L et al (2002) Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position. Nature 416(6876):94–99PubMedCrossRefGoogle Scholar
  81. Reijmers RM, Vondenhoff MF, Roozendaal R et al (2010) Impaired lymphoid organ development in mice lacking the heparan sulfate modifying enzyme glucuronyl C5-epimerase. J Immunol 184(7):3656–3664PubMedCrossRefGoogle Scholar
  82. Richardson TP, Peters MC, Ennett AB et al (2001) Polymeric system for dual growth factor delivery. Nat Biotechnol 19(11):1029–1034PubMedCrossRefGoogle Scholar
  83. Rodgers KD, San Antonio JD, Jacenko O (2008) Heparan sulfate proteoglycans: a GAGgle of skeletal-hematopoietic regulators. Dev Dyn 237(10):2622–2642PubMedPubMedCentralCrossRefGoogle Scholar
  84. Roozendaal R, Mebius RE (2011) Stromal cell-immune cell interactions. Annu Rev Immunol 29:23–43PubMedCrossRefGoogle Scholar
  85. Ruddle NH, Akirav EM (2009) Secondary lymphoid organs: responding to genetic and environmental cues in ontogeny and the immune response. J Immunol 183(4):2205–2212PubMedPubMedCentralCrossRefGoogle Scholar
  86. Saito Y, Uchida N, Tanaka S et al (2010) Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML. Nat Biotechnol 28(3):275–280PubMedGoogle Scholar
  87. Salomonsson S, Jonsson MV, Skarstein K et al (2003) Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjogren’s syndrome. Arthritis Rheum 48(11):3187–3201PubMedCrossRefGoogle Scholar
  88. Shi K, Hayashida K, Kaneko M et al (2001) Lymphoid chemokine B cell-attracting chemokine-1 (CXCL13) is expressed in germinal center of ectopic lymphoid follicles within the synovium of chronic arthritis patients. J Immunol 166(1):650–655PubMedCrossRefGoogle Scholar
  89. Shields JD, Kourtis IC, Tomei AA et al (2010) Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. Science 328:749–752PubMedCrossRefGoogle Scholar
  90. Shultz LD, Lyons BL, Burzenski LM et al (2005) Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol 174(10):6477–6489PubMedCrossRefGoogle Scholar
  91. Shultz LD, Ishikawa F, Greiner DL (2007) Humanized mice in translational biomedical research. Nat Rev Immunol 7(2):118–130PubMedCrossRefGoogle Scholar
  92. Shultz LD, Saito Y, Najima Y et al (2010) Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2r gamma (null) humanized mice. Proc Natl Acad Sci U S A 107(29):13022–13027PubMedPubMedCentralCrossRefGoogle Scholar
  93. Shultz LD, Brehm MA, Garcia-Matinez JV et al (2012) Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol 12:786–798PubMedPubMedCentralCrossRefGoogle Scholar
  94. Stachowiak AN, Irvine DJ (2008) Inverse opal hydrogel-collagen composite scaffolds as a supportive microenvironment for immune cell migration. J Biomed Mater Res A 85(3):815–828PubMedCrossRefGoogle Scholar
  95. Stott DI, Hiepe F, Hummel M et al (1998) Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease. The salivary glands of patients with Sjogren’s syndrome. J Clin Invest 102(5):938–946PubMedPubMedCentralCrossRefGoogle Scholar
  96. Suematsu S, Watanabe T (2004) Generation of a synthetic lymphoid tissue-like organoid in mice. Nat Biotechnol 22(12):1539–1545PubMedCrossRefGoogle Scholar
  97. Sun Z, Unutmaz D, Zou YR et al (2000) Requirement for RORgamma in thymocyte survival and lymphoid organ development. Science 288(5475):2369–2373PubMedCrossRefGoogle Scholar
  98. Sun Q, Chen RR, Shen Y (2005) Sustained vascular endothelial growth factor delivery enhances angiogenesis and perfusion in ischemic hind limb. Pharm Res 22(7):1110–1116PubMedCrossRefGoogle Scholar
  99. Takebe T, Sekine K, Enomura M et al (2013) Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499:481–485PubMedCrossRefGoogle Scholar
  100. Takebe T, Enomura M, Yoshizawa E et al (2015) Vascularized and complex organ buds from diverse tissues via mesenchymal cell-derived condensation. Cell Stem Cell 16:556–565PubMedCrossRefGoogle Scholar
  101. Takemura S, Braun A, Crowson C et al (2001) Lymphoid neogenesis in rheumatoid synovitis. J Immunol 167(2):1072–1080PubMedCrossRefGoogle Scholar
  102. Tan J, Watanabe T (2014) Murine spleen tissue regeneration from neonatal spleen capsule requires lymphotoxin priming of stromal cells. J Immunol 193:1194–1203PubMedPubMedCentralCrossRefGoogle Scholar
  103. Teng YD, Lavik EB, Qu X et al (2002) Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc Natl Acad Sci U S A 99(5):3024–3029PubMedPubMedCentralCrossRefGoogle Scholar
  104. Thaunat O, Field AC, Dai J et al (2005) Lymphoid neogenesis in chronic rejection: evidence for a local humoral alloimmune response. Proc Natl Acad Sci U S A 102(41):14723–14728PubMedPubMedCentralCrossRefGoogle Scholar
  105. Thomas JA, Willcox HN, Newsom-Davis J (1982) Immunological studies of the thymus in myasthenia gravis. Correction with clinical state and thymocyte culture responses. J Neuroimmunol 3(4):319–335PubMedCrossRefGoogle Scholar
  106. Thompson ED, Enriquez HL, Fu YX et al (2010) Tumor masses support naive T cell infiltration, activation, and differentiation into effectors. J Exp Med 207(8):1791–1804PubMedPubMedCentralCrossRefGoogle Scholar
  107. Tomei AA, Siegert S, Britschgi MR et al (2009) Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node microenvironment. J Immunol 183(7):4273–4283PubMedCrossRefGoogle Scholar
  108. Traggiai E, Chicha L, Mazzucchelli L et al (2004) Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 304(5667):104–107PubMedCrossRefGoogle Scholar
  109. Ugel S, Zoso A, De Santo C et al (2009) In vivo administration of artificial antigen-presenting cells activates low-avidity T cells for treatment of cancer. Cancer Res 69(24):9376–9384PubMedPubMedCentralCrossRefGoogle Scholar
  110. Van De Pavert SA, Olivier BJ, Goverse G et al (2009) Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation. Nat Immunol 10(11):1193–1199PubMedPubMedCentralCrossRefGoogle Scholar
  111. Vondenhoff MF, Greuter M, Goverse G et al (2009) LTbetaR signaling induces cytokine expression and up-regulates lymphangiogenic factors in lymph node anlagen. J Immunol 182(9):5439–5445PubMedPubMedCentralCrossRefGoogle Scholar
  112. Weiss JM, Cufi P, Le Panse R et al (2013) The thymus in autoimmune Myasthenia Gravis: paradigm for a tertiary lymphoid organ. Rev Neurol (Paris) 169(8):640–649CrossRefGoogle Scholar
  113. Willfuhr KU, Westermann J, Pabst R (1992) Splenic autotransplantation provides protection against fatal sepsis in young but not in old rats. J Pediatr Surge 27(9):1207–1212CrossRefGoogle Scholar
  114. Yokota Y, Mansouri A, Mori S (1999) Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2. Nature 397:702–706PubMedCrossRefGoogle Scholar
  115. Young CL, Adamson TC 3rd, Vaughan JH et al (1984) Immunohistologic characterization of synovial membrane lymphocytes in rheumatoid arthritis. Arthritis Rheum 27(1):32–39PubMedCrossRefGoogle Scholar
  116. Yu X, Bellamkonda RV (2003) Tissue-engineered scaffolds are effective alternatives to autografts for bridging peripheral nerve gaps. Tissue Eng 9(3):421–430PubMedCrossRefGoogle Scholar
  117. Yu X, Botchwey EA, Levine EM et al (2004) Bioreactor-based bone tissue engineering: the influence of dynamic flow on osteoblast phenotypic expression and matrix mineralization. Proc Natl Acad Sci U S A 101(31):11203–11208PubMedPubMedCentralCrossRefGoogle Scholar
  118. Zeng M, Palardini M, Engram JC et al (2012) Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution. Blood 120(9):1856–1867PubMedPubMedCentralCrossRefGoogle Scholar
  119. Zhang L, Kovalev GI, Su L (2007) HIV-1 infection and pathogenesis in a novel humanized mouse model. Blood 109(7):2978–2981PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Japan 2016

Authors and Affiliations

  • Yuka Kobayashi
    • 1
  • Koichi Kato
    • 2
  • Makoto Nakamura
    • 3
  • Takeshi Watanabe
    • 1
  1. 1.The Tazuke-Kofukai Medical Research Institute/Kitano HospitalKita-kuJapan
  2. 2.Department of Biomaterials Science, Graduate School of Biomedical ScienceUniversity of HiroshimaMinami-kuJapan
  3. 3.Faculty of Life Science and EngineeringUniversity of ToyamaToyamaJapan

Personalised recommendations