Chronic Inflammation Caused by Lymphotoxin is Lymphoid Neogenesis

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1996 Apr 1

PMID 8666904

Citations 155

Authors

A Kratz

A Campos-Neto

M S Hanson

N H Ruddle

Affiliations

Soon will be listed here.

Abstract

In presenting a unifying concept for chronic inflammation and lymphoid organogenesis, we suggest that lymphotoxin's (LT, LT-alpha, TNF-beta) crucial role in these processes is pivotal and similar. Chronic inflammatory lesions that developed in the kidney and pancreas at the sites of transgene expression in rat insulin promoter-LT (RIP-LT) mice resembled lymph nodes with regard to cellular composition (T cells, B cells, plasma cells, and antigen-presenting cells), delineated T and B cell areas, primary and secondary follicles, characteristic morphologic and antigenic (ICAM-1, VCAM-1, MAdCAM-1, and PNAd) features of high endothelial venules, and ability to respond to antigen and undergo Ig class switching when obtained from mice immunized with SRBC. The vascular changes, with the exception of PNAd, appear to be the direct consequence of transgene derived LT expression, as they were also observed in RIP-LT mice lacking mature T and B cells. These data show that LT-induced chronic inflammation has the characteristics of organized lymphoid tissue.

Citing Articles

The prognostic significance of tertiary lymphoid structures in oral squamous cell carcinomas: a systematic review.

Ribeiro V, Teillaud J, Dieu-Nosjean M, Lescaille G, Rochefort J Front Oral Health. 2025; 5:1524313.

PMID: 39911478 PMC: 11794802. DOI: 10.3389/froh.2024.1524313.

Modulation of Lymphotoxin β Surface Expression by Kaposi's Sarcoma-Associated Herpesvirus K3 Through Glycosylation Interference.

Kang S, Brulois K, Choi Y, Zhang S, Jung J J Med Virol. 2025; 97(1):e70179.

PMID: 39831393 PMC: 11744495. DOI: 10.1002/jmv.70179.

IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.

Amisaki M, Zebboudj A, Yano H, Zhang S, Payne G, Chandra A Nature. 2025; 638(8052):1076-1084.

PMID: 39814891 PMC: 11864983. DOI: 10.1038/s41586-024-08426-5.

Tertiary Lymphoid Structures and Immunotherapy: Challenges and Opportunities.

Ruddle N Methods Mol Biol. 2024; 2864:299-312.

PMID: 39527229 DOI: 10.1007/978-1-0716-4184-2_16.

Mouse Models Enable the Functional Investigation of Tertiary Lymphoid Structures in Cancer.

Jeevanandam A, Yin Z, Connolly K, Joshi N Methods Mol Biol. 2024; 2864:57-76.

PMID: 39527217 DOI: 10.1007/978-1-0716-4184-2_4.

References

Picker L, Butcher E . Physiological and molecular mechanisms of lymphocyte homing. Annu Rev Immunol. 1992; 10:561-91. DOI: 10.1146/annurev.iy.10.040192.003021. View

Allison J, Malcolm L, Chosich N, Miller J . Inflammation but not autoimmunity occurs in transgenic mice expressing constitutive levels of interleukin-2 in islet beta cells. Eur J Immunol. 1992; 22(5):1115-21. DOI: 10.1002/eji.1830220503. View

Picarella D, Kratz A, Li C, Ruddle N, Flavell R . Insulitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas. Proc Natl Acad Sci U S A. 1992; 89(21):10036-40. PMC: 50272. DOI: 10.1073/pnas.89.21.10036. View

Higuchi Y, Herrera P, Muniesa P, Huarte J, Belin D, Ohashi P . Expression of a tumor necrosis factor alpha transgene in murine pancreatic beta cells results in severe and permanent insulitis without evolution towards diabetes. J Exp Med. 1992; 176(6):1719-31. PMC: 2119473. DOI: 10.1084/jem.176.6.1719. View

Picarella D, Kratz A, Li C, Ruddle N, Flavell R . Transgenic tumor necrosis factor (TNF)-alpha production in pancreatic islets leads to insulitis, not diabetes. Distinct patterns of inflammation in TNF-alpha and TNF-beta transgenic mice. J Immunol. 1993; 150(9):4136-50. View

Ohashi P, Oehen S, Aichele P, Pircher H, Odermatt B, Herrera P . Induction of diabetes is influenced by the infectious virus and local expression of MHC class I and tumor necrosis factor-alpha. J Immunol. 1993; 150(11):5185-94. View

Pozzilli P, Signore A, Williams A, Beales P . NOD mouse colonies around the world--recent facts and figures. Immunol Today. 1993; 14(5):193-6. DOI: 10.1016/0167-5699(93)90160-M. View

Lehmann P, Sercarz E, Forsthuber T, Dayan C, GAMMON G . Determinant spreading and the dynamics of the autoimmune T-cell repertoire. Immunol Today. 1993; 14(5):203-8. DOI: 10.1016/0167-5699(93)90163-F. View

Wogensen L, Huang X, Sarvetnick N . Leukocyte extravasation into the pancreatic tissue in transgenic mice expressing interleukin 10 in the islets of Langerhans. J Exp Med. 1993; 178(1):175-85. PMC: 2191087. DOI: 10.1084/jem.178.1.175. View

10.

Stewart T, Hultgren B, Huang X, Hully J, MacLachlan N . Induction of type I diabetes by interferon-alpha in transgenic mice. Science. 1993; 260(5116):1942-6. DOI: 10.1126/science.8100367. View

11.

Mooij P, de Wit H, Drexhage H . An excess of dietary iodine accelerates the development of a thyroid-associated lymphoid tissue in autoimmune prone BB rats. Clin Immunol Immunopathol. 1993; 69(2):189-98. DOI: 10.1006/clin.1993.1169. View

12.

Crowley M, Inaba K, Steinman R . Macrophages, but not dendritic cells, accumulate colloidal carbon following administration in situ. J Cell Sci. 1993; 105 ( Pt 4):965-73. DOI: 10.1242/jcs.105.4.965. View

13.

Hanninen A, Taylor C, Streeter P, Stark L, Sarte J, Shizuru J . Vascular addressins are induced on islet vessels during insulitis in nonobese diabetic mice and are involved in lymphoid cell binding to islet endothelium. J Clin Invest. 1993; 92(5):2509-15. PMC: 288436. DOI: 10.1172/JCI116859. View

14.

Sikorski E, Hallmann R, Berg E, Butcher E . The Peyer's patch high endothelial receptor for lymphocytes, the mucosal vascular addressin, is induced on a murine endothelial cell line by tumor necrosis factor-alpha and IL-1. J Immunol. 1993; 151(10):5239-50. View

15.

Ge A, Butcher E . Cloning and expression of a cDNA encoding mouse endoglin, an endothelial cell TGF-beta ligand. Gene. 1994; 138(1-2):201-6. DOI: 10.1016/0378-1119(94)90808-7. View

16.

DE TOGNI P, Goellner J, Ruddle N, Streeter P, Fick A, Mariathasan S . Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 1994; 264(5159):703-7. DOI: 10.1126/science.8171322. View

17.

Barten D, Ruddle N . Vascular cell adhesion molecule-1 modulation by tumor necrosis factor in experimental allergic encephalomyelitis. J Neuroimmunol. 1994; 51(2):123-33. DOI: 10.1016/0165-5728(94)90074-4. View

18.

Guerder S, Picarella D, Linsley P, Flavell R . Costimulator B7-1 confers antigen-presenting-cell function to parenchymal tissue and in conjunction with tumor necrosis factor alpha leads to autoimmunity in transgenic mice. Proc Natl Acad Sci U S A. 1994; 91(11):5138-42. PMC: 43947. DOI: 10.1073/pnas.91.11.5138. View

19.

Faveeuw C, Gagnerault M, Lepault F . Expression of homing and adhesion molecules in infiltrated islets of Langerhans and salivary glands of nonobese diabetic mice. J Immunol. 1994; 152(12):5969-78. View

20.

Chen Y, Kuchroo V, Inobe J, Hafler D, Weiner H . Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science. 1994; 265(5176):1237-40. DOI: 10.1126/science.7520605. View