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Human CD(4+)CD(25+) regulatory T cells and infectious tolerance.
Michael Stassen1, Edgar Schmitt, Helmut Jonuleit
1Institute of Immunology, Johannes Gutenberg-University, Mainz, Germany. michael.stassen@gmx.de.
Transplantation
|January 17, 2004
Summary
Regulatory T cells (Treg) control autoaggressive T cells to maintain peripheral tolerance. Distinct Treg subsets induce specific T helper suppressor (Th(sup)) cells via cell contact, producing IL-10 or TGF-beta for immune regulation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Regulatory T cells (Treg) are crucial for peripheral tolerance by controlling autoaggressive T cells.
- Different T cell subsets, including induced T helper type 3 (Th3), T regulatory type 1 (Tr1), and naturally occurring CD4+CD25+ Treg, exhibit suppressive properties.
Purpose of the Study:
- To investigate the mechanisms by which human CD4+CD25+ Treg subsets mediate immune suppression.
- To characterize the distinct properties of T helper suppressor (Th(sup)) cells generated by different Treg subsets.
Main Methods:
- Analysis of human CD4+CD25+ Treg subsets expressing alpha4beta7 or alpha4beta1 integrins.
- Assessment of Treg-mediated suppression and the generation of Th(sup) cells.
- Detection of cytokine production (IL-10 and TGF-beta) by Th(sup) cells.
Main Results:
- Two subsets of human CD4+CD25+ Treg were identified based on integrin expression: alpha4beta7 Treg and alpha4beta1 Treg.
- alpha4beta7 Treg induced Tr1-like Th(sup) cells producing interleukin-10 (IL-10).
- alpha4beta1 Treg induced Th3-like Th(sup) cells producing transforming growth factor-beta (TGF-beta).
Conclusions:
- Human CD4+CD25+ Treg subsets differentially induce Th(sup) cells with distinct suppressive cytokine profiles.
- This study reconciles in vitro contact-dependent suppression with in vivo soluble factor-mediated (IL-10 and TGF-beta) immune regulation.