Modulation by cytokines of induction of oral tolerance to type II collagen

GJ Thorbecke, R Schwarcz, J Leu… - … : Official Journal of …, 1999 - Wiley Online Library
GJ Thorbecke, R Schwarcz, J Leu, C Huang, WJ Simmons
Arthritis & Rheumatism: Official Journal of the American College …, 1999Wiley Online Library
Objective To determine whether the simultaneous administration of drugs and/or cytokines
such as transforming growth factor β (TGFβ) can render oral tolerance to type II collagen
(CII) more effective in causing resistance to collagen‐induced arthritis (CIA) in mice, and to
investigate whether oral tolerance can still be induced when high levels of anti‐CII are
present. Methods Tolerance was induced by intragastric feeding of low‐dose CII to DBA/1
mice during a 2‐week period, either before immunization with CII in Freund's complete …
Objective
To determine whether the simultaneous administration of drugs and/or cytokines such as transforming growth factor β (TGFβ) can render oral tolerance to type II collagen (CII) more effective in causing resistance to collagen‐induced arthritis (CIA) in mice, and to investigate whether oral tolerance can still be induced when high levels of anti‐CII are present.
Methods
Tolerance was induced by intragastric feeding of low‐dose CII to DBA/1 mice during a 2‐week period, either before immunization with CII in Freund's complete adjuvant or after initiation of arthritis. Some mice were simultaneously injected with TGFβ1 or with the H2 receptor agonist dimaprit.
Results
Both TGFβ1 and dimaprit increased the degree of oral tolerance obtained. TGFβ1 augmented the induction of immunoregulatory CD8 T cells, which transferred the resistance to CIA induction to normal recipients. Feeding of CII for 2 weeks, starting after the onset of arthritis, still significantly ameliorated the course of CIA.
Conclusion
Administration of TGFβ1 or dimaprit, both of which are believed to promote the development of immunoregulatory T cells, may reinforce induction of oral tolerance, even after the onset of arthritis.
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