CD4+CD25+ regulatory T cells limit the risk of autoimmune disease arising from T cell receptor crossreactivity.
The molecular-mimicry theory proposes that immune crossreactivity between microbial and self-antigen is the initiating event in the activation of autoaggressive immune responses leading to autoimmune disease. In support of this possibility, it is now accepted that T cell recognition of antigen is highly degenerate. However, it is to be expected that the immune system would have evolved mechanisms to counter such a potential danger. We studied the influence of CD4(+)CD25(+) regulatory T cells (Treg) on the ability of suboptimal T cell receptor ligands to provoke autoimmunity. By using CD4(+) T cell-driven experimental autoimmune encephalomyelitis as a model, it was found that depletion of CD4(+)CD25(+)Foxp3(+) Treg allowed pathology to develop in response to suboptimal T cell stimulation. These data demonstrate the importance of Treg in raising the threshold of triggering of autoreactive T cell responses, thus limiting the risk of autoimmune disease due to molecular mimicry.
Stephens
Leigh A
LA
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, UK. leigh.stephens@ed.ac.uk
Gray
David
D
Anderton
Stephen M
SM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D003429:Cross Reactions / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D018716:Molecular Mimicry / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D008024:Ligands; D010455:Peptides; D011948:Receptors, Antigen, T-Cell