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Cytokines and peripheral tolerance to alloantigen
M J Dallman1, K J Wood, K Hamano
1University of Oxford, Nuffield Department of Surgery, John Radcliffe Hospital, Headington, England.
Immunological Reviews
|June 1, 1993
Summary
Peripheral tolerance involves altered cytokine production, with decreased IL-2 and IFN-gamma, and increased IL-10 and IL-4. Manipulating cytokine balance, possibly via CD28/CTLA-4-B7 interactions, may induce and maintain this tolerance.
Area of Science:
- Immunology
- Transplantation immunology
Background:
- Peripheral tolerance to alloantigen is crucial for transplant success.
- Altered cytokine profiles, including reduced IL-2 and IFN-gamma and increased IL-10 and IL-4, are observed in tolerant states.
Purpose of the Study:
- To investigate the causal relationship between altered cytokine production and the induction/maintenance of peripheral tolerance.
- To explore alternative methods for influencing cytokine balance to achieve tolerance.
Main Methods:
- Analysis of cytokine production patterns (IL-2, IFN-gamma, IL-10, IL-4) in tolerant animals.
- Review of experiments involving selective IL-2 blockade with CD25 antibodies.
- Consideration of CD28/CTLA-4-B7 interaction pathways.
Main Results:
- A decrease in IL-2 and IFN-gamma, alongside sustained IL-10 and IL-4, accompanies peripheral tolerance.
- Blocking IL-2 action suggests cytokine manipulation is a viable route to tolerance.
- CD28/CTLA-4-B7 interactions present a potential approach for influencing cytokine balance.
Conclusions:
- Altered cytokine profiles are associated with peripheral tolerance to alloantigen.
- Targeting cytokine production, potentially through CD28/CTLA-4-B7 pathways, offers promising strategies for inducing and maintaining transplant tolerance.