Continuous nasal administration of antigen is critical to maintain tolerance in adoptively transferred autoimmune arthritis in SCID mice

T. Bárdos, M. Czipri, C. Vermes, J. Zhang, K. Mikecz, T. T. Glant

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Mucosal tolerance is a natural mechanism that prevents immunological reactions to antigens by altering the activity of immune cells of pathogenic clones without modulating the entire immune system. This 'natural immune suppression' can be exploited when antigen(s) of the target organ in an autoimmune disease is used for mucosal treatment. Being inspired by the experimental results in animal models, clinical trials using type II collagen for mucosal treatment have been conducted in rheumatoid arthritis. High-density proteoglycan (aggrecan) is another major macromolecular component in articular cartilage, and may be a candidate autoantigen for provoking immune reactions in patients with rheumatoid arthritis. Indeed, like type II collagen, systemic immunization of genetically susceptible mice with proteoglycan (PG) aggrecan induces progressive autoimmune polyarthritis. Here, we investigated whether intranasally applied PG can be effective in suppressing PG-induced arthritis (PGIA) in BALB/c mice. We found that nasal administration of 100 μg PG exerted a strong suppressive effect on both the incidence and severity of the disease, most probably by reducing responsiveness towards the immunizing PG antigen. When we transferred PGIA into genetically matched but immunodeficient SCID mice, we were able to establish a tolerized state, but only if the recipient SCID mice received lymphocytes from tolerized animals and intranasal treatment with PG was continued. Without nasally administered antigen, the transferred anergic cells recovered and arthritis rapidly developed in a severe form. Intranasal PG treatment of recipient SCID mice was ineffective when cells from non-tolerized arthritic donors were transferred, in which case the regular weekly 'tolerizing' dose of PG made the disease worse. Our results suggest that mucosal treatment in an already existing disease may result in paradoxical outcomes.

Original languageEnglish
Pages (from-to)224-231
Number of pages8
JournalClinical and Experimental Immunology
Volume129
Issue number2
DOIs
Publication statusPublished - 2002

Fingerprint

Intranasal Administration
SCID Mice
Proteoglycans
Arthritis
Antigens
Aggrecans
Collagen Type II
Rheumatoid Arthritis
Therapeutics
Autoantigens
Articular Cartilage
Autoimmune Diseases
Immune System
Immunization
Animal Models
Clone Cells
Tissue Donors
Clinical Trials
Lymphocytes

Keywords

  • Autoimmune arthritis
  • Nasal tolerance
  • Proteoglycan
  • SCID
  • Transfer

ASJC Scopus subject areas

  • Immunology

Cite this

Continuous nasal administration of antigen is critical to maintain tolerance in adoptively transferred autoimmune arthritis in SCID mice. / Bárdos, T.; Czipri, M.; Vermes, C.; Zhang, J.; Mikecz, K.; Glant, T. T.

In: Clinical and Experimental Immunology, Vol. 129, No. 2, 2002, p. 224-231.

Research output: Contribution to journalArticle

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