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MHC-II-independent CD4+ T cells induce colitis in immunodeficient RAG-/- hosts
Z Trobonjaca1, F Leithäuser, P Möller
1Department of Medical Microbiology and Immunology, University of Ulm, Ulm, Germany.
Journal of Immunology (Baltimore, Md. : 1950)
|March 10, 2001
Summary
CD4(+) T cells can induce severe inflammatory bowel disease (IBD) in mice, regardless of MHC-II dependence. However, MHC-II-dependent CD4(+) T cells require MHC-II to fully express their IBD-inducing potential.
Area of Science:
- Immunology
- Gastroenterology
- T cell biology
Background:
- Inflammatory bowel disease (IBD) pathogenesis is complex.
- The role of CD4(+) T cells and their interaction with MHC molecules in IBD is not fully understood.
Purpose of the Study:
- To investigate the capacity of different CD4(+) T cell subsets to induce IBD.
- To determine the MHC restriction and T cell receptor usage in IBD-inducing CD4(+) T cells.
Main Methods:
- Engraftment of T cells from various knockout mouse models into immunodeficient RAG1(-/-) hosts.
- Analysis of inflammatory infiltrates in the colon.
- Characterization of cytokine production (TNF-alpha, IFN-gamma, IL-4, IL-10) and T cell activation markers (CD69, CD44, CD28).
Main Results:
- CD4(+) T cells from normal, MHC-II-deficient, and CD1d-deficient mice induced IBD.
- MHC-II-dependent CD4(+) T cells induced Th1 responses and required MHC-II for full IBD induction.
- MHC-II-independent CD4(+) T cells also induced colitis, with distinct cytokine profiles.
Conclusions:
- Both MHC-II-dependent and -independent CD4(+) T cells can induce severe IBD.
- MHC-II-dependent CD4(+) T cells require MHC-II to exert their full pathogenic potential in IBD.
- These findings reveal novel insights into IBD mechanisms involving T cell-MHC interactions.