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Preferential Th1 immune response in invariant chain-deficient mice
Ian Topilski1, Alon Harmelin, Richard A Flavell
1Department of Immunology and Experimental Animal Center, The Weizmann Institute of Science, Rehovot, Israel.
Journal of Immunology (Baltimore, Md. : 1950)
|February 2, 2002
Summary
Invariant chain (Ii) deficiency in mice leads to normal CD4(+) T cell proliferation but altered cytokine profiles. These mice exhibit a selective Th1 immune response, lacking a Th2 response, suggesting impaired antigen presentation.
Area of Science:
- Immunology
- Molecular Biology
Background:
- MHC class II molecules interact with the invariant chain (Ii) during biosynthesis.
- Ii plays crucial roles in MHC class II folding, peptide association, and transport.
Purpose of the Study:
- To investigate the immune response in invariant chain-deficient (Ii(-/-)) mice.
- To determine the role of Ii in T cell responses and antigen presentation.
Main Methods:
- In vitro and in vivo immune response assessment in Ii(-/-) mice.
- Analysis of CD4(+) T cell proliferation and cytokine secretion (IFN-gamma, IL-4).
- Evaluation of Th1 and Th2 responses using delayed-type hypersensitivity, TNBS colitis, and asthma models.
Main Results:
- CD4(+) T cells from Ii(-/-) mice showed normal proliferation but skewed cytokine secretion towards IFN-gamma.
- Ii(-/-) mice mounted normal Th1 responses in DTH and colitis models.
- A significant lack of Th2 response was observed in Ii(-/-) mice during an asthma model.
Conclusions:
- Defective antigen presentation in Ii(-/-) mice selectively promotes a Th1 effector response.
- The invariant chain is critical for balancing Th1 and Th2 immune responses.