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Active suppression induced by anti-CD4

P R Hutchings¹, A Cooke, K Dawe

¹Immunology Department, University College and Middlesex Medical School, London.

European Journal of Immunology

|April 1, 1993

Summary

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Treating mice with a special antibody prevented autoimmune thyroiditis. This protective effect was transferable, showing that the antibody treatment created immune cells that could suppress the disease in other mice.

Area of Science:

Immunology
Autoimmunity
Thyroid Research

Background:

Murine autoimmune thyroiditis is a model for human autoimmune thyroid diseases.
CD4+ T cells play a critical role in the pathogenesis of autoimmune thyroiditis.

Purpose of the Study:

To investigate the efficacy of non-depleting anti-CD4 monoclonal antibody treatment in preventing murine autoimmune thyroiditis.
To determine if the induced unresponsiveness is antigen-specific and mediated by suppressive immune cells.

Main Methods:

Treatment of mice with a non-depleting anti-CD4 monoclonal antibody in the presence of mouse thyroglobulin (MTg).
Transfer of immune cells from treated mice to lightly irradiated recipients.
Challenge of recipients with specific antigen to assess suppression of thyroiditis.

Related Experiment Videos

Analysis of anti-MTg autoantibody production to evaluate helper T cell subset involvement.

Main Results:

Treatment with anti-CD4 antibody significantly inhibited the development of murine autoimmune thyroiditis.
Unresponsiveness was transferable, indicating the generation of suppressive donor cells.
Suppression was antigen-specific and antigen-dependent.
No significant effect on anti-MTg autoantibodies was observed, suggesting a selective impact on T helper cell subsets.

Conclusions:

Non-depleting anti-CD4 antibody treatment can induce antigen-specific tolerance in experimental autoimmune thyroiditis.
This tolerance is mediated by the generation of antigen-specific suppressive T cells.
The mechanism of suppression may involve a selective targeting of T helper cell subsets involved in autoantibody production.