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Altered immune responses in interleukin 10 transgenic mice
A Hagenbaugh1, S Sharma, S M Dubinett
1Molecular Biology Institute, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.
The Journal of Experimental Medicine
|June 16, 1997
Summary
Transgenic mice overexpressing Interleukin-10 (IL-10) showed impaired anti-tumor immunity but maintained resistance to Leishmania infection. This suggests IL-10
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Interleukin-10 (IL-10) is a cytokine that suppresses immune responses.
- Altered IL-10 expression impacts autoimmune disease, infections, and tumor immunity.
- Understanding IL-10's role requires models with controlled expression.
Purpose of the Study:
- To investigate the effects of IL-10 overexpression on immune responses.
- To develop transgenic mice with IL-10 expression driven by the IL-2 promoter.
- To assess the impact on autoimmune models, infectious agents, and tumor growth.
Main Methods:
- Developed IL-10 transgenic mice using the IL-2 promoter.
- Stimulated spleen cells in vitro to measure cytokine production (IL-10, IFN-gamma).
- Transferred T cells to assess colitis development and Leishmania major resistance.
- Evaluated tumor growth and immune response in vivo.
Main Results:
- Transgenic mice exhibited higher IL-10 and lower IFN-gamma production.
- IL-10 overexpression prevented T cell-induced colitis and tumor growth.
- Resistance to Leishmania major infection was retained.
- Blocking IL-10 antibodies restored anti-tumor responses.
Conclusions:
- Altered T cell cytokine profiles, specifically IL-10 overexpression, significantly impact immune responses.
- The effects of IL-10 are stimulus-dependent, affecting inflammation and anti-tumor immunity.
- These transgenic mice are valuable tools for studying IL-10-mediated immunity.