Total dose and frequency of administration critically affect success of nasal mucosal tolerance induction

Hui-Rong Jiang, N. Taylor, Linda Duncan, A. D. Dick, John Vincent Forrester

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Aims-Nasal tolerance induction with autoantigens can effectively protect against a variety of experimental models of autoimmune disease. The aims of this study were to characterise the dosage and kinetics of inhibition of experimental autoimmune uveoretinitis (EAU) via intranasal administration of the uveitogenic antigen interphotoreceptor retinal binding protein (IRBP) in the murine model of IRBP induced EAU.

Methods-B10RIII mice were tolerised by intranasal administration of IRBP either with a long term multiple low dose or a short term/high dosing regimen before subcutaneous immunisation with IRBP in complete Freund's adjuvant (CFA). On day 15 post-immunisation, mice were killed and eyes were removed for histological examination and quantification of inflammatory cell infiltration and degree of target organ (rod outer segment, ROS) destruction.

Results-Nasal administration of multiple low doses of IRBP (1 mug or 3 mug IRBP per mouse per day for 10 days) significantly protected mice fi om IRBP induced EAU. Short term/high dose regimens were only effective when given either as a single or, art most, as two consecutive doses (40 mug per dose). Multiple doses in the range of 45-120 mug over 3 days afforded no protection.

Conclusions-These results indicate that both dose and frequency of intranasal antigen administration are pivotal to tolerance induction and subsequent suppression of T cell mediated autoimmune disease.

Original languageEnglish
Pages (from-to)739-744
Number of pages5
JournalBritish Journal of Ophthalmology
Volume85
Issue number6
DOIs
Publication statusPublished - 2001

Keywords

  • EXPERIMENTAL AUTOIMMUNE UVEORETINITIS
  • MYELIN BASIC-PROTEIN
  • CD4(+) T-CELLS
  • GROWTH-FACTOR-BETA
  • ORAL TOLERANCE
  • MYASTHENIA-GRAVIS
  • IMMUNOLOGICAL-TOLERANCE
  • ACETYLCHOLINE-RECEPTOR
  • RETINAL ANTIGENS
  • MURINE MODEL

Equipment

Iain Fraser Cytometry Centre

Andrea Holme (Manager), Linda Duncan (Senior Application Scientist), Ailsa Laird (Technician) & Kate Burgoyne (Technician)

Institute of Medical Sciences

Research Facilities: Facility

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