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Rheumatology 2002; 41: 775-779
© 2002 British Society for Rheumatology

Original Papers

Dynamics of mycobacterial HSP65-induced T-cell cytokine expression during oral tolerance induction in adjuvant arthritis

P. M. Cobelens, A. Kavelaars, R. van der Zee1, W. van Eden1 and C. J. Heijnen

Department of Immunology, Wilhelmina Children's Hospital of the University Medical Center Utrecht and
1 Department of Infectious Disease and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands

Objective. To investigate whether oral administration of mycobacterial heat-shock protein 65 (HSP65) during adjuvant arthritis (AA) induces regulatory cells and cytokines.

Methods. AA was induced in Lewis rats and from the time of disease onset HSP65 in the presence of soya bean trypsin inhibitor (STI) was administered orally every other day. The number of splenic CD4+CD25+ T cells and antigen-induced cytokine mRNA expression were determined.

Results. Oral treatment with HSP65/STI reduced AA symptoms. After one feeding of HSP65/STI, the number of CD4+CD25+ splenic T cells increased and HSP65-specific T cells expressed increased levels of interferon {gamma} and interleukin 10. After two feedings, the expression of interleukin-10 mRNA remained increased, whereas there was low expression of interferon {gamma} mRNA. The number of CD4+CD25+ splenic T cells remained increased.

Conclusions. Oral treatment with HSP65/STI after AA onset reduces disease symptoms via dynamic changes in the number of CD4+CD25+ splenocytes and in antigen-induced cytokine production.

KEY WORDS: Arthritis, Tolerance, HSP65, Tr1, CD25.

Correspondence to: C. J. Heijnen, Department of Immunology, Wilhelmina Children's Hospital of the University Medical Center Utrecht, Room KC3.68.0, Lundlaan 6, 3584 EA Utrecht, The Netherlands.


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