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. 1999 Aug;65(2):294–301. doi: 10.1086/302517

Unlinking tumor necrosis factor biology from the major histocompatibility complex: lessons from human genetics and animal models.

S R Ruuls 1, J D Sedgwick 1
PMCID: PMC1377927  PMID: 10417271

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bazzoni F., Beutler B. The tumor necrosis factor ligand and receptor families. N Engl J Med. 1996 Jun 27;334(26):1717–1725. doi: 10.1056/NEJM199606273342607. [DOI] [PubMed] [Google Scholar]
  2. Bean A. G., Roach D. R., Briscoe H., France M. P., Korner H., Sedgwick J. D., Britton W. J. Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin. J Immunol. 1999 Mar 15;162(6):3504–3511. [PubMed] [Google Scholar]
  3. Brinkman B. M., Huizinga T. W., Kurban S. S., van der Velde E. A., Schreuder G. M., Hazes J. M., Breedveld F. C., Verweij C. L. Tumour necrosis factor alpha gene polymorphisms in rheumatoid arthritis: association with susceptibility to, or severity of, disease? Br J Rheumatol. 1997 May;36(5):516–521. doi: 10.1093/rheumatology/36.5.516. [DOI] [PubMed] [Google Scholar]
  4. Brinkman B. M., Zuijdeest D., Kaijzel E. L., Breedveld F. C., Verweij C. L. Relevance of the tumor necrosis factor alpha (TNF alpha) -308 promoter polymorphism in TNF alpha gene regulation. J Inflamm. 1995;46(1):32–41. [PubMed] [Google Scholar]
  5. Bélanger A., Hum D. W., Beaulieu M., Lévesque E., Guillemette C., Tchernof A., Bélanger G., Turgeon D., Dubois S. Characterization and regulation of UDP-glucuronosyltransferases in steroid target tissues. J Steroid Biochem Mol Biol. 1998 Apr;65(1-6):301–310. doi: 10.1016/s0960-0760(97)00183-0. [DOI] [PubMed] [Google Scholar]
  6. Czermak B. J., Sarma V., Bless N. M., Schmal H., Friedl H. P., Ward P. A. In vitro and in vivo dependency of chemokine generation on C5a and TNF-alpha. J Immunol. 1999 Feb 15;162(4):2321–2325. [PubMed] [Google Scholar]
  7. Feldmann M., Charles P., Taylor P., Maini R. N. Biological insights from clinical trials with anti-TNF therapy. Springer Semin Immunopathol. 1998;20(1-2):211–228. doi: 10.1007/BF00832008. [DOI] [PubMed] [Google Scholar]
  8. Frei K., Eugster H. P., Bopst M., Constantinescu C. S., Lavi E., Fontana A. Tumor necrosis factor alpha and lymphotoxin alpha are not required for induction of acute experimental autoimmune encephalomyelitis. J Exp Med. 1997 Jun 16;185(12):2177–2182. doi: 10.1084/jem.185.12.2177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fu Y. X., Chaplin D. D. Development and maturation of secondary lymphoid tissues. Annu Rev Immunol. 1999;17:399–433. doi: 10.1146/annurev.immunol.17.1.399. [DOI] [PubMed] [Google Scholar]
  10. Galli-Taliadoros L. A., Sedgwick J. D., Wood S. A., Körner H. Gene knock-out technology: a methodological overview for the interested novice. J Immunol Methods. 1995 Apr 12;181(1):1–15. doi: 10.1016/0022-1759(95)00017-5. [DOI] [PubMed] [Google Scholar]
  11. Gerlai R. Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? Trends Neurosci. 1996 May;19(5):177–181. doi: 10.1016/s0166-2236(96)20020-7. [DOI] [PubMed] [Google Scholar]
  12. Gruen J. R., Weissman S. M. Evolving views of the major histocompatibility complex. Blood. 1997 Dec 1;90(11):4252–4265. [PubMed] [Google Scholar]
  13. Hodgson H. Prospects of new therapeutic approaches for Crohn's disease. Lancet. 1999 Feb 6;353(9151):425–426. doi: 10.1016/S0140-6736(98)00304-3. [DOI] [PubMed] [Google Scholar]
  14. Jacob C. O., Fronek Z., Lewis G. D., Koo M., Hansen J. A., McDevitt H. O. Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1233–1237. doi: 10.1073/pnas.87.3.1233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Karpus W. J., Ransohoff R. M. Chemokine regulation of experimental autoimmune encephalomyelitis: temporal and spatial expression patterns govern disease pathogenesis. J Immunol. 1998 Sep 15;161(6):2667–2671. [PubMed] [Google Scholar]
  16. Kassiotis G., Pasparakis M., Kollias G., Probert L. TNF accelerates the onset but does not alter the incidence and severity of myelin basic protein-induced experimental autoimmune encephalomyelitis. Eur J Immunol. 1999 Mar;29(3):774–780. doi: 10.1002/(SICI)1521-4141(199903)29:03<774::AID-IMMU774>3.0.CO;2-T. [DOI] [PubMed] [Google Scholar]
  17. Kontoyiannis D., Pasparakis M., Pizarro T. T., Cominelli F., Kollias G. Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies. Immunity. 1999 Mar;10(3):387–398. doi: 10.1016/s1074-7613(00)80038-2. [DOI] [PubMed] [Google Scholar]
  18. Körner H., Cook M., Riminton D. S., Lemckert F. A., Hoek R. M., Ledermann B., Köntgen F., Fazekas de St Groth B., Sedgwick J. D. Distinct roles for lymphotoxin-alpha and tumor necrosis factor in organogenesis and spatial organization of lymphoid tissue. Eur J Immunol. 1997 Oct;27(10):2600–2609. doi: 10.1002/eji.1830271020. [DOI] [PubMed] [Google Scholar]
  19. Körner H., Riminton D. S., Strickland D. H., Lemckert F. A., Pollard J. D., Sedgwick J. D. Critical points of tumor necrosis factor action in central nervous system autoimmune inflammation defined by gene targeting. J Exp Med. 1997 Nov 3;186(9):1585–1590. doi: 10.1084/jem.186.9.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Liu J., Marino M. W., Wong G., Grail D., Dunn A., Bettadapura J., Slavin A. J., Old L., Bernard C. C. TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination. Nat Med. 1998 Jan;4(1):78–83. doi: 10.1038/nm0198-078. [DOI] [PubMed] [Google Scholar]
  21. Mackay F., Bourdon P. R., Griffiths D. A., Lawton P., Zafari M., Sizing I. D., Miatkowski K., Ngam-ek A., Benjamin C. D., Hession C. Cytotoxic activities of recombinant soluble murine lymphotoxin-alpha and lymphotoxin-alpha beta complexes. J Immunol. 1997 Oct 1;159(7):3299–3310. [PubMed] [Google Scholar]
  22. McDermott M. F., Aksentijevich I., Galon J., McDermott E. M., Ogunkolade B. W., Centola M., Mansfield E., Gadina M., Karenko L., Pettersson T. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell. 1999 Apr 2;97(1):133–144. doi: 10.1016/s0092-8674(00)80721-7. [DOI] [PubMed] [Google Scholar]
  23. Ngo V. N., Korner H., Gunn M. D., Schmidt K. N., Riminton D. S., Cooper M. D., Browning J. L., Sedgwick J. D., Cyster J. G. Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J Exp Med. 1999 Jan 18;189(2):403–412. doi: 10.1084/jem.189.2.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pasparakis M., Alexopoulou L., Episkopou V., Kollias G. Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J Exp Med. 1996 Oct 1;184(4):1397–1411. doi: 10.1084/jem.184.4.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Peschon J. J., Torrance D. S., Stocking K. L., Glaccum M. B., Otten C., Willis C. R., Charrier K., Morrissey P. J., Ware C. B., Mohler K. M. TNF receptor-deficient mice reveal divergent roles for p55 and p75 in several models of inflammation. J Immunol. 1998 Jan 15;160(2):943–952. [PubMed] [Google Scholar]
  26. Sacca R., Cuff C. A., Lesslauer W., Ruddle N. H. Differential activities of secreted lymphotoxin-alpha3 and membrane lymphotoxin-alpha1beta2 in lymphotoxin-induced inflammation: critical role of TNF receptor 1 signaling. J Immunol. 1998 Jan 1;160(1):485–491. [PubMed] [Google Scholar]
  27. Sean Riminton D., Körner H., Strickland D. H., Lemckert F. A., Pollard J. D., Sedgwick J. D. Challenging cytokine redundancy: inflammatory cell movement and clinical course of experimental autoimmune encephalomyelitis are normal in lymphotoxin-deficient, but not tumor necrosis factor-deficient, mice. J Exp Med. 1998 May 4;187(9):1517–1528. doi: 10.1084/jem.187.9.1517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smyth M. J., Kelly J. M., Baxter A. G., Körner H., Sedgwick J. D. An essential role for tumor necrosis factor in natural killer cell-mediated tumor rejection in the peritoneum. J Exp Med. 1998 Nov 2;188(9):1611–1619. doi: 10.1084/jem.188.9.1611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Stuber F., Udalova I. A., Book M., Drutskaya L. N., Kuprash D. V., Turetskaya R. L., Schade F. U., Nedospasov S. A. -308 tumor necrosis factor (TNF) polymorphism is not associated with survival in severe sepsis and is unrelated to lipopolysaccharide inducibility of the human TNF promoter. J Inflamm. 1995;46(1):42–50. [PubMed] [Google Scholar]
  30. Suen W. E., Bergman C. M., Hjelmström P., Ruddle N. H. A critical role for lymphotoxin in experimental allergic encephalomyelitis. J Exp Med. 1997 Oct 20;186(8):1233–1240. doi: 10.1084/jem.186.8.1233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tessier P. A., Naccache P. H., Clark-Lewis I., Gladue R. P., Neote K. S., McColl S. R. Chemokine networks in vivo: involvement of C-X-C and C-C chemokines in neutrophil extravasation in vivo in response to TNF-alpha. J Immunol. 1997 Oct 1;159(7):3595–3602. [PubMed] [Google Scholar]
  32. Theofilopoulos A. N. The basis of autoimmunity: Part II. Genetic predisposition. Immunol Today. 1995 Mar;16(3):150–159. doi: 10.1016/0167-5699(95)80133-2. [DOI] [PubMed] [Google Scholar]
  33. Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol. 1992;10:411–452. doi: 10.1146/annurev.iy.10.040192.002211. [DOI] [PubMed] [Google Scholar]
  34. Wilson A. G., Symons J. A., McDowell T. L., McDevitt H. O., Duff G. W. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3195–3199. doi: 10.1073/pnas.94.7.3195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wilson A. G., di Giovine F. S., Duff G. W. Genetics of tumour necrosis factor-alpha in autoimmune, infectious, and neoplastic diseases. J Inflamm. 1995;45(1):1–12. [PubMed] [Google Scholar]

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