Differential modulation of CNS-specific effector and regulatory T cells during tolerance induction by recombinant invariant chains in vivo.

Abstract

Inflammation within the Central Nervous System (CNS) is largely controlled by the balance between CNS-specific effector and regulatory T lymphocytes. To suppress CNS-inflammation in an antigen-specific manner, CNS-specific effector and regulatory T cells thus have to be differentially regulated. We employed recombinant peptide/MHC class II tetramers to assess CNS-specific effector and regulatory T cells during the specific suppression of myelin proteolipid protein aa139-151 (PLP139-151)-induced experimental autoimmune encephalomyelitis (EAE) by intravenous injection of recombinant invariant chains (Ii) in which the CLIP region has been replaced by the PLP139-151 epitope (Ii-PLP139-151). Injection of Ii-PLP139-151 induced apoptosis in CNS-specific effector T cells. In contrast, the proportion of specific regulatory T cells was increased and these cells expressed larger amounts of molecules that mediate regulatory T cell function including transforming growth factor beta and the inducible costimulator (ICOS). Consequently, regulatory T cells from Ii-treated mice were more potent than regulatory T cells from control-treated animals in suppressing effector T cell proliferation. These data demonstrate that effector T cells and regulatory T cells directed against the same CNS-antigen can be differentially regulated in vivo to suppress CNS-autoimmunity. Recombinant Ii induce apoptosis in CNS-specific effector T cells and provoke qualitative changes in specific regulatory T cells that enhance their immunosuppressive properties.

• Authors: Christian Lange, Hong Doster, Karin Steinbach, Hubert Kalbacher, Matthias Scholl, Arthur Melms, Felix Bischof
• Journal: Brain, behavior, and immunity (Brain Behav Immun) Vol. 23 Issue 6 Pg. 861-7 (Aug 2009) ISSN: 1090-2139 [Electronic] Netherlands
• PMID: 19362139 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• Caspase 3

Topics

• Adoptive Transfer
• Animals
• Apoptosis (drug effects)
• CD4-Positive T-Lymphocytes (immunology)
• Caspase 3 (biosynthesis, genetics)
• Central Nervous System (cytology, immunology)
• Encephalomyelitis, Autoimmune, Experimental (immunology)
• Flow Cytometry
• Genes, MHC Class II (immunology)
• Immune Tolerance (physiology)
• Lymph Nodes (cytology, drug effects)
• Mice
• Recombinant Proteins (chemistry, pharmacology)
• T-Lymphocytes (immunology)
• T-Lymphocytes, Regulatory (immunology)
• Th2 Cells (immunology)