CD4+CD25+ regulatory T cells are activated in vivo by recognition of self.
Naturally occurring CD4(+)CD25(+) regulatory T cells (nT(R)) comprise a separate lineage of T cells that are essential for maintaining immunological tolerance to self. Here we demonstrate that the level of phosphorylation of the TCR zeta-chain is approximately 1.5- to 4-fold higher in nT(R) as compared with CD4(+)CD25(-) T cells. The increased level of TCR zeta-chain phosphorylation is presumably secondary to their higher affinity for self, resulting in a stronger TCR signal as it was completely blocked by treatment with anti-MHC class II. The enhanced level of TCR zeta-chain phosphorylation was correlated with the capacity of nT(R) to develop non-specific suppressor effector function following culture with IL-2 or IL-4 in the absence of TCR stimulus. Thus, a sub-population of nT(R) is activated by recognition of self-peptide-MHC class II ligands in vivo, resulting in their capacity to be induced to mediate suppressor function in vitro in the absence of TCR stimulation.
Andersson
John
J
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institute of Health, 10 Center Drive, MSC-1892, Bethesda, MD 20892-1892, USA.
Stefanova
Irena
I
Stephens
Geoffrey L
GL
Shevach
Ethan M
EM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001324:Autoantigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004527:Egg Proteins / Q000276:immunology; D005260:Female; D006388:Hemagglutinins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D004527:Egg Proteins; D006388:Hemagglutinins; D000949:Histocompatibility Antigens Class II; C474482:I-A(b) antigen, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D008565:Membrane Proteins; C110366:OVA-8; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D015847:Interleukin-4; D010047:Ovalbumin