Skip to main content

Advertisement

SpringerLink
Log in

Interferon-τ

Prospects for Clinical Use in Autoimmune Disorders

  • Review Article
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Interferon-tau (IFN-τ) is a type I IFN originally discovered for its role as a pregnancy recognition hormone in ruminant animals such as sheep and cows. IFN-τ possesses all of the biological properties ascribed to the other type I IFNs including antiviral, antiproliferative and immunomodulatory activities. However, IFN-τ differs in that it is relatively nontoxic to cells at high concentrations as compared to the toxicity normally associated with IFNs-α and -β and the type II IFN, IFN-γ.

IFN-τ was examined for its ability to prevent the development of experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), in humans. IFN-τ prevents development of EAE as effectively as IFN-β, a type I IFN currently being used for the treatment of MS. Unlike IFN-β, however, IFN-τ treated mice did not develop leucopenia or experience bodyweight loss indicative of toxicity.

Superantigens can induce relapses in EAE, similar to those that are observed in patients with relapsing-remitting MS; IFN-τ blocks superantigen reactivation of EAE. The inhibitory effect of IFN-τ on induction of EAE and reactivation by superantigen involves suppression of myelin basic protein and superantigen activation of T cells as well as suppressed induction of inflammatory cytokines such as tumour necrosis factor-alpha. In addition, IFN-τ has been shown to reduce immunologically mediated spontaneous fetal resorption. Thus, IFN-τ has considerable potential for treatment of autoimmune and immunologically mediated disorders, including MS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bazer FW, Johnson HM. Type I conceptus interferons: maternal recognition of pregnancy signals and potential therapeutic agents. Am J Reprod Immunol 1991; 26: 19–22

    PubMed  CAS  Google Scholar 

  2. Johnson HM, Bazer FW, Szente BE, et al. How interferons fight disease. Sci Am 1994; 270: 40–7

    Article  Google Scholar 

  3. Pontzer CH, Bazer FB, Johnson HM. Antiproliferative activity of a pregnancy recognition hormone, ovine trophoblast pro- tein-1. Cancer Res 1991; 51: 5304–7

    PubMed  CAS  Google Scholar 

  4. Soos JM, Subramian PS, Hobeika AC, et al. The interferon pregnancy recognition hormone, interferon tau, blocks both development and superantigen reactivation of experimental allergic encephalomyelitis without associated toxicity. J Immunol 1995; 155: 2747–53

    PubMed  CAS  Google Scholar 

  5. Soos JM, Mustafa MG, Subramanian PS, et al. Oral feeding of intereron /gt can prevent acute and chronic relapsing forms of experimental allergic encephalomyelitis. J Neuroimmunol 1997; 75: 43–50

    Article  PubMed  CAS  Google Scholar 

  6. Zamvil SS, Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Ann Rev Immunol 1990; 8: 579–621

    Article  CAS  Google Scholar 

  7. Martal J, Lacroix MC, Loudes C, et al. Trophoblastin, an anti-luteolytic protein present in early pregnancy in sheep. J Reprod Fertil 1979; 56: 63–73

    Article  PubMed  CAS  Google Scholar 

  8. Godkin JD, Bazer FB, Moffatt J, et al. Purification and properties of a major, low molecular weight protein released by the trophoblast of sheep blastocysts at day 13-21. J Reprod Fertil 1982; 65: 141–50

    Article  PubMed  CAS  Google Scholar 

  9. Vallet JL, Bazer FW, Fliss MFV, et al. Effect of ovine conceptus secretory proteins and purified ovine trophoblast protein-1 on interoestrous interval and plasma concentrations of prosta-glandin F2alpha and E and of 13,14-dihydro-15-keto prosta-glandin F2alpha in cyclic ewes. J Reprod Fertil 1988; 84: 493–504

    Article  PubMed  CAS  Google Scholar 

  10. Godkin JD, Bazer FB, Thatcher WW, et al. Proteins released by cultured day 15-16 conceptuses prolong luteal maintenance when introduced into the uterine lumen of cyclic ewes. J Reprod Fertil 1984; 71: 57–64

    Article  PubMed  CAS  Google Scholar 

  11. Vallet JL, Bazer FW, Ashworth CJ, et al. Development of a radioimmunoassay for ovine trophoblast protein-1, the anti-luteolytic protein from the sheep conceptus. J Endocrinol 1988; 117: R5–R8

    Article  PubMed  CAS  Google Scholar 

  12. Flint APF, Sheldrick EL, McCann TJ, et al. Luteal oxytocin: characteristics and control of synchronous episodes of oxytocin and PGF2alpha secretion at luteolysis in ruminants. Dornest Anim Endocrinol 1990; 7: 111–24

    Article  CAS  Google Scholar 

  13. Mirando MA, Ott TL, Harney JP, et al. Ovine trophoblast protein-one inhibits development of endometrial responsiveness to oxytocin in ewes. Biol Reprod 1990; 43: 1070–8

    Article  PubMed  CAS  Google Scholar 

  14. Bazer FW, Spencer TE, Ott TL. Interferon tau: a novel pregnancy recognition signal. Am J Reprod Immunol 1997; 37: 412–20

    Article  PubMed  CAS  Google Scholar 

  15. Bartol FF, Roberts RM, Bazer FW, et al. Characterization of proteins produced in vitro by peri-attachment bovine concep-tuses. Biol Reprod 1985; 32: 681–93

    Article  PubMed  CAS  Google Scholar 

  16. Gnatek GG, Smith LD, Duby RT, et al. Maternal recognition of pregnancy in the goat: effects of conceptus removal on inter-estrus intervals and characterization of conceptus protein production during early pregnancy. Biol Reprod 1989; 41: 655–64

    Article  PubMed  CAS  Google Scholar 

  17. Liu L, Leaman DW, Roberts RM. The interferon-tau genes of the giraffe, a nonbovid species. J IFN Cytokine Res 1996; 16: 949–51

    Article  CAS  Google Scholar 

  18. Roberts RM, Cross JC, Leaman DW. Interferons as hormones of pregnancy. Endocrinol Rev 1992; 13: 432–52

    CAS  Google Scholar 

  19. Imakawa K, Anthony RV, Kazemi M, et al. Interferon-like sequence of ovine trophoblast protein secreted by embryonic trophectoderm. Nature 1987; 330: 377–9

    Article  PubMed  CAS  Google Scholar 

  20. Stewart HJ, McCann SHE, Northorp AJ, et al. Sheep anti-luteolytic interferon: cDNA sequence and analysis of mRNA levels. J Mol Endocrinol 1989; 2: 65–70

    Article  PubMed  CAS  Google Scholar 

  21. Klemann SW, Imakawa K, Roberts RM. Sequence variability among ovine trophoblast interferon mRNA. Nucleic Acids Res 1990; 18: 6724

    Article  PubMed  CAS  Google Scholar 

  22. Charlier M, Hue D, Boisnard M, et al. Cloning and structural analysis of two distinct families of ovine interferon-alpha genes encoding functional class II and trophoblast (oTP-1) alpha-interferons. Mol Cell Endocrinol 1991; 76: 161–71

    Article  PubMed  CAS  Google Scholar 

  23. Jarpe MA, Johnson HM, Bazer FW, et al. Predicted structural motif of IFN tau. Protein Eng 1994; 7: 863–7

    Article  PubMed  CAS  Google Scholar 

  24. Pontzer CH, Torres B A, Vallet JL, et al. Antiviral activity of the pregnancy recognition ovine trophoblast protein-1. Biochem Biophys Res Comm 1988; 152: 801–7

    Article  PubMed  CAS  Google Scholar 

  25. Mirando MA, Short EC, Geisert RD, et al. Stimulation of 2,5-oligodenylate synthetase activity in sheep endometrium during pregnancy, by intrauterine infusion ofoTP-1, and by intramuscular administration of recombinant bovine inter-feron-alphal. J Reprod Fertil 1991; 93: 599

    Article  PubMed  CAS  Google Scholar 

  26. Dereuddre-Bosquet N, Clayette P, Martin M, et al. Anti-HIV potential of a new interferon, interferon-tau (trophoblastin). J AIDS Human Retrovirol 1996; 11: 241–6

    CAS  Google Scholar 

  27. Pontzer CH, Yamamoto JK, Bazer FB, et al. Potent anti-feline immunodeficiency virus and anti-human immunodeficiency virus effect of interferon-tau. J Immunol 1997; 158: 4351–7

    PubMed  CAS  Google Scholar 

  28. Soos JM, Johnson HM. Type I interferon inhibition of super-antigen-induced stimulation: implications for the treatment of superantigen associated disease. J IFN Cytokine Res 1995; 15: 39–45

    Article  CAS  Google Scholar 

  29. Skopets B, Li J, Thatcher WW, et al. Inhibition of lymphocyte proliferation by bovine trophoblast protein-1 (type I trophoblast interferon) and bovine interferon-alphal. Vet Immunol Immunopathol 1992; 34: 81–96

    Article  PubMed  CAS  Google Scholar 

  30. Cross JC, Roberts RM. Constitutive and trophoblast-specific expression of a class of bovine interferon genes. Proc Natl Acad Sci USA 1991; 88: 3817–21

    Article  PubMed  CAS  Google Scholar 

  31. Hansen TR, Kazemi M, Keisler DH, et al. Complex binding of the embryonic interferon, ovine trophoblast protein-1, to en-dometrial receptors. J IFN Res 1989; 9: 215–25

    CAS  Google Scholar 

  32. Stewart HJ, McCann SHE, Lamming GE, et al. Evidence for a role for interferon in the maternal recognition of pregnancy. J Reprod Fertil 1989; 37 Suppl: 127–38

    Google Scholar 

  33. Pontzer CH, Ott TL, Bazer FW, et al. Structure/function studies with interferon tau: evidence for multiple active sites. J IFN Res 1994; 14: 133–41

    CAS  Google Scholar 

  34. Whaley AE, Reddy Meka CS, Hunt JS, et al. Identification and cellular localization of unique interferon mRNA from human placenta. J Biol Chem 1994; 269: 10864–8

    PubMed  CAS  Google Scholar 

  35. Langford MP, Stanton GJ, Johnson HM. Biological effects of staphylococcal enterotoxin on human peripheral lymphocytes. Infect Immun 1978; 22: 62–8

    PubMed  CAS  Google Scholar 

  36. Carlsson R, Sjogren HO. Kinetics of IL-2 and interferon production, expression of IL-2 receptors, and cell proliferation in human mononuclear cells exposed to staphylococcal enterotoxin A. Cell Immunol 1985; 96: 175–83

    Article  PubMed  CAS  Google Scholar 

  37. Johnson HM, Magazine HI. Potent mitogenic activity of staphylococcal enterotoxin A requires induction of IL-2. Int Arch Allergy Appl Immunol 1988; 87: 87–90

    Article  PubMed  CAS  Google Scholar 

  38. Bergdoll MS, Crass BA, Reiser RF, et al. A new staphylococcal enterotoxin F, associated with toxic shock syndrome Staphy-lococcus aureus isolates. Lancet 1981; I: 1071–2

    Google Scholar 

  39. Johnson HM, Torres B A, Soos JM. Superantigens: structure and relevance to human disease. Proc Soc Exp Biol Med 1996; 212: 99–109

    PubMed  CAS  Google Scholar 

  40. White J, Herman A, Pullen AM, et al. The Vβ specific super-antigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell 1989; 56: 27–35

    Article  PubMed  CAS  Google Scholar 

  41. Carlsson R, Fischer H, Sjogren HO. Binding of staphylococcal enterotoxin A to accessory cells is a requirement for its ability to activate human T cells. J Immunol 1988; 140: 2484–8

    PubMed  CAS  Google Scholar 

  42. Fleischer B, Schrezenmeier H. T cell stimulation by staphylococcal enterotoxins. Clonally variable response and requirement for major histocompatibility complex class II molecules on accessory or target cells. J Exp Med 1988; 176: 1697–707

    Article  Google Scholar 

  43. Panitch HS, Hirsch RL, Haley AS, et al. Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet 1987; I: 893–5

    Article  Google Scholar 

  44. Panitch HS, Hirsch RL, Schindler J, et al. Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system. Neurology 1987; 37: 1097–102

    Article  PubMed  CAS  Google Scholar 

  45. Powell MB, Mitchell D, Lederman J, et al. Lymphotoxin and tumor necrosis factor alpha production by myelin basic protein specific T cell clones correlates with encephalitogenicity. Int Immunol 1990; 2: 539–44

    Article  PubMed  CAS  Google Scholar 

  46. Selmaj KW, Raine CS. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 1988; 23: 339–46

    Article  PubMed  CAS  Google Scholar 

  47. Fritz RB, Chou CH, McFarlin DE. Relapsing murine experimental allergic encephalomyelitis induced by myelin basic protein. J Immunol 1983; 130: 1024–6

    PubMed  CAS  Google Scholar 

  48. Schiffenbauer J, Johnson HM, Butfiloski E, et al. Staphylococcal enterotoxins reactivate experimental allergic encephalomyelitis. Proc Natl Acad Sci 1993; 90: 8543–6

    Article  PubMed  CAS  Google Scholar 

  49. Soos JM, Schiffenbauer J, Johnson HM. Treatment of PL/J mice with the superantigen, staphycoccal enterotoxin B, prevents development of experimental allergic encephalomyelitis. J Neuroimmunol 1993; 43: 39–43

    Article  PubMed  CAS  Google Scholar 

  50. Kaiman B, Lublin FD, Lattime E, et al. Effects of staphylococcal enterotoxin B on T cell receptor Vβ utilization and clinical manifestations of experimental allergic encephalomyelitis. J Neuroimmunol 1993; 45: 83–8

    Article  Google Scholar 

  51. Soos JM, Hobeika AC, Butfiloski EJ, et al. Accelerated induction of experimental allergic encephalomyelitis in PL/J mice by a non-Vβ8-specific superantigen. Proc Natl Acad Sci USA 1995; 92: 6082–6

    Article  PubMed  CAS  Google Scholar 

  52. Schiffenbauer J, Soos JM, Johnson HM. The possible role of bacterial superantigens in the pathogenesis of autoimmune disorders. Immunol Today 1998; 19: 117–20

    PubMed  CAS  Google Scholar 

  53. IFNβ Multiple Sclerosis Study Group. Interferon IFNβ-lb is effective in relapsing-remitting multiple sclerosis. Clinical results of a multicenter, randomized, double blind, placebo controlled trial. Neurology 1993; 43: 655–61

    Article  Google Scholar 

  54. Rudick RA, Goodkin DE, Jacobs LD, et al. Impact of interferon beta-la on neurologic disability in relapsing multiple sclerosis. Neurology 1997; 49: 358–63

    Article  PubMed  CAS  Google Scholar 

  55. Weinstock-Guttman B, Ransohoff RM, Kinkel RP, et al. The interferons: biological effects, mechanisms of action, and use in multiple sclerosis. Ann Neurol 1995; 37: 7–15

    Article  PubMed  CAS  Google Scholar 

  56. Mujtaba MG, Soos JM, Johnson HM. CD4 T suppressor cells mediate interferon tau protection against experimental allergic encephalomyelitis. J Neuroimmunol 1997; 75: 35–42

    Article  PubMed  CAS  Google Scholar 

  57. Mattsson R, Holmdahl R, Scheynius A, et al. Placental MHC class I antigen expression is induced in mice following in vivo treatment with recombinant interferon gamma. J Reprod Immunol 1991; 19: 115–29

    Article  PubMed  CAS  Google Scholar 

  58. Tezabwala BU, Johnson PM, Rees RC. Inhibition of pregnancy viability in mice following IL-2 administration. Immunology 1989; 67: 115–9

    PubMed  CAS  Google Scholar 

  59. Lin H, Mossman TR, Guilbert L, et al. Synthesis of T helper 2 cytokines at the maternal fetal interface. J Immunol 1993; 151: 4562–73

    PubMed  CAS  Google Scholar 

  60. Assal-Meliani A, Kinsky R, Martal J. In. vivo immunosuppressin effects of recombinant ovine interferon-tau (trophoblastin): r.oTP (r.oIFN-t) inhibits local GVH reaction in mice (PLN assay), prevents fetal resoptions, and favors embryo survival and implantation in the CBA/J X DBA mice combination. Am J Reprod Immunol 1995; 33: 267–75

    PubMed  CAS  Google Scholar 

  61. Chaouat G, Assal-Meliani A, Martal J, et al. IL-10 prevents naturally occurring fetal loss in the CBA X DBA mating combination, and local defect in IL-10 production in this abortion prone combination is corrected by in vivo injection of IFN-tau. J Immunol 1995; 154: 4261–8

    PubMed  CAS  Google Scholar 

  62. Degre M. Influence of exogenous interferon on the peripheral white blood cell count in mice. Int J Cancer 1974; 14: 699–703

    Article  PubMed  CAS  Google Scholar 

  63. Fent K, Zbinden G. Toxicity of interferon and interleukin. Trends Pharmacol Sci 1987; 8: 100–5

    Article  CAS  Google Scholar 

  64. David M, Larner AC. Activation of transcription factors by in-terferon-alpha in a cell free system. Science 1992; 257: 813–5

    Article  PubMed  CAS  Google Scholar 

  65. Schindler C, Shuai K, Prezioso VR, et al. Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science 1992; 257: 813–5

    Article  Google Scholar 

  66. Valazquez L, Fellous M, Stark GR, et al. A protein tyrosine kinase in the interferon a/β signaling pathway. Cell 1992; 70: 313–22

    Article  Google Scholar 

  67. Ihle JN, Witthuhn B A, Quelle FW, et al. Signaling by the cytokine receptor family: JAKs and STATs. Trends Biol Sci 1994; 19: 222–7

    Article  CAS  Google Scholar 

  68. Subramaniam PS, Khan SA, Pontzer CH, et al. Differential recognition of the type I interferon receptor by interferons tau and alpha is responsible for their disparate cytotoxicities. Proc Natl Acad Sci USA 1995; 92: 12270–4

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital, Avenue Louis Pasteur, 02115, Boston, MA, USA

    Jeanne M. Soos

  2. Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, USA

    Howard M. Johnson

Authors
  1. Jeanne M. Soos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Howard M. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeanne M. Soos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Soos, J.M., Johnson, H.M. Interferon-τ. BioDrugs 11, 125–135 (1999). https://doi.org/10.2165/00063030-199911020-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-199911020-00006

Keywords

Search

Navigation