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CD8 T cell clones inhibit antitumor T cell function by secreting IL-10
1University of South Alabama College of Medicine, Department of Microbiology and Immunology, Mobile 36688, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|December 15, 1995
Summary
Irradiated mice develop enhanced tumor growth and produce noncytotoxic CD8+ T cells that suppress immune responses. These cells secrete IL-10, inhibiting cytotoxic T cells and potentially inducing T cell anergy.
Area of Science:
- Immunology
- Cancer Research
- T cell Biology
Background:
- Irradiated mice exhibit accelerated tumor development.
- Splenic oncofetal (OFA)-specific, noncytotoxic CD8+ T cells were isolated from these mice.
- These T cells secrete a factor inhibiting cytotoxic T cell activity against lymphoma cells.
Purpose of the Study:
- To investigate the mechanism by which noncytotoxic CD8+ T cells inhibit immune responses.
- To determine the role of cytokines, specifically IL-10, in this suppression.
- To explore the potential of IL-10 in inducing T cell anergy.
Main Methods:
- Cloning of splenic noncytotoxic CD8+ T cells.
- In vitro assays measuring cytotoxic T cell activity and proliferation.
- Cytokine analysis of T cell culture supernatants.
- Neutralization of IL-10 using monoclonal antibodies.
Main Results:
- Noncytotoxic CD8+ T cell supernatants inhibited cytotoxic T cell killing and IFN-gamma secretion.
- IL-10 was identified in the supernatants of noncytotoxic CD8+ T cells but not cytotoxic T cells.
- Anti-IL-10 antibodies restored cytotoxic activity and IFN-gamma secretion.
- IL-10 mediated the inhibition in a dose-dependent and non-specific manner.
Conclusions:
- IL-10 secreted by noncytotoxic CD8+ T cells suppresses effector T cell function.
- IL-10 may play a critical role in inducing T cell anergy in the context of tumor immunity.
- Targeting IL-10 could be a therapeutic strategy in enhancing anti-tumor responses.