Lymph Node Stroma Broaden the Peripheral Tolerance Paradigm

Overview

Journal Trends Immunol

Specialty Allergy & Immunology

Date 2010 Dec 15

PMID 21147035

Citations 64

Authors

Anne L Fletcher

Deepali Malhotra

Shannon J Turley

Affiliations

Soon will be listed here.

Abstract

Research into how self-reactive T cells are tolerized in lymph nodes has focused largely on dendritic cells (DCs). We now know that lymph node stromal cells (LNSC) are important mediators of deletional tolerance to peripheral tissue-restricted antigens (PTAs), which are constitutively expressed and presented by LNSCs. Of the major LNSC subsets, fibroblastic reticular cells and lymphatic endothelial cells are known to directly induce tolerance of responding naïve CD8 T cells. The biological outcome of this interaction fills a void otherwise not covered by DCs or thymic stromal cells. These findings, we suggest, necessitate a broadening of peripheral tolerance theory to include steady-state presentation of clinically relevant PTA to naïve CD8 T cells by lymph node-resident stroma.

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References

Orimo A, Gupta P, Sgroi D, Arenzana-Seisdedos F, Delaunay T, Naeem R . Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell. 2005; 121(3):335-48. DOI: 10.1016/j.cell.2005.02.034. View

Mueller S, Matloubian M, Clemens D, Sharpe A, Freeman G, Gangappa S . Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection. Proc Natl Acad Sci U S A. 2007; 104(39):15430-5. PMC: 2000533. DOI: 10.1073/pnas.0702579104. View

Zhang R, Ma A, Urbanski S, McCafferty D . Induction of inducible nitric oxide synthase: a protective mechanism in colitis-induced adenocarcinoma. Carcinogenesis. 2006; 28(5):1122-30. DOI: 10.1093/carcin/bgl224. View

Hammerschmidt S, Ahrendt M, Bode U, Wahl B, Kremmer E, Forster R . Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo. J Exp Med. 2008; 205(11):2483-90. PMC: 2571923. DOI: 10.1084/jem.20080039. View

Timmer T, Baltus B, Vondenhoff M, Huizinga T, Tak P, Verweij C . Inflammation and ectopic lymphoid structures in rheumatoid arthritis synovial tissues dissected by genomics technology: identification of the interleukin-7 signaling pathway in tissues with lymphoid neogenesis. Arthritis Rheum. 2007; 56(8):2492-502. DOI: 10.1002/art.22748. View

Baddoura F, Nasr I, Wrobel B, Li Q, Ruddle N, Lakkis F . Lymphoid neogenesis in murine cardiac allografts undergoing chronic rejection. Am J Transplant. 2005; 5(3):510-6. DOI: 10.1111/j.1600-6143.2004.00714.x. View

Katakai T, Hara T, Lee J, Gonda H, Sugai M, Shimizu A . A novel reticular stromal structure in lymph node cortex: an immuno-platform for interactions among dendritic cells, T cells and B cells. Int Immunol. 2004; 16(8):1133-42. DOI: 10.1093/intimm/dxh113. View

Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts A . Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008; 2(2):141-50. DOI: 10.1016/j.stem.2007.11.014. View

Fletcher A, Lukacs-Kornek V, Reynoso E, Pinner S, Bellemare-Pelletier A, Curry M . Lymph node fibroblastic reticular cells directly present peripheral tissue antigen under steady-state and inflammatory conditions. J Exp Med. 2010; 207(4):689-97. PMC: 2856033. DOI: 10.1084/jem.20092642. View

10.

Shields J, Kourtis I, Tomei A, Roberts J, Swartz M . Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. Science. 2010; 328(5979):749-52. DOI: 10.1126/science.1185837. View

11.

Gonzalez-Rey E, Anderson P, Gonzalez M, Rico L, Buscher D, Delgado M . Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. Gut. 2009; 58(7):929-39. DOI: 10.1136/gut.2008.168534. View

12.

Gallegos A, Bevan M . Central tolerance to tissue-specific antigens mediated by direct and indirect antigen presentation. J Exp Med. 2004; 200(8):1039-49. PMC: 2211843. DOI: 10.1084/jem.20041457. View

13.

Martinez-Outschoorn U, Balliet R, Rivadeneira D, Chiavarina B, Pavlides S, Wang C . Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells. Cell Cycle. 2010; 9(16):3256-76. PMC: 3041164. DOI: 10.4161/cc.9.16.12553. View

14.

Koble C, Kyewski B . The thymic medulla: a unique microenvironment for intercellular self-antigen transfer. J Exp Med. 2009; 206(7):1505-13. PMC: 2715082. DOI: 10.1084/jem.20082449. View

15.

Vezys V, Olson S, Lefrancois L . Expression of intestine-specific antigen reveals novel pathways of CD8 T cell tolerance induction. Immunity. 2000; 12(5):505-14. DOI: 10.1016/s1074-7613(00)80202-2. View

16.

Tokuda N, Adachi T, Adachi Y, Higashi M, Sharifi K, Tuerxun T . Identification of FABP7 in fibroblastic reticular cells of mouse lymph nodes. Histochem Cell Biol. 2010; 134(5):445-52. DOI: 10.1007/s00418-010-0754-2. View

17.

Tomei A, Siegert S, Britschgi M, Luther S, Swartz M . Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node microenvironment. J Immunol. 2009; 183(7):4273-83. DOI: 10.4049/jimmunol.0900835. View

18.

Bajenoff M, Egen J, Koo L, Laugier J, Brau F, Glaichenhaus N . Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity. 2006; 25(6):989-1001. PMC: 2692293. DOI: 10.1016/j.immuni.2006.10.011. View

19.

Link A, Vogt T, Favre S, Britschgi M, Acha-Orbea H, Hinz B . Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat Immunol. 2007; 8(11):1255-65. DOI: 10.1038/ni1513. View

20.

Allan R, Waithman J, Bedoui S, Jones C, Villadangos J, Zhan Y . Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity. 2006; 25(1):153-62. DOI: 10.1016/j.immuni.2006.04.017. View