Antigen-based therapies targeting the expansion of regulatory T cells in autoimmune and allergic disease.
Between 5 and 10% of the European population suffer from autoimmune disease, whilst allergic disorders affect an even higher frequency, and both these forms of immunopathology have increased markedly in recent decades. The need for more precise and effective therapeutic strategies drives the investigation of antigen-based tolerance in rodent models and in patients. The identification of the key role T-regulatory cells (Tregs) play in avoidance of immunopathology focused on either self or environmental antigens has led to a need to determine whether established and novel tolerance-inducing strategies are in fact expanding antigenreactive Treg populations. Here we review recent data from mouse and man. A consistent thread is that, both in T-helper (Th)1/Th17-driven autoimmune disease and in Th2-driven allergic disease, antigen-based tolerance induction often promotes an antigen-reactive IL-10 T-cell population whilst reducing the pathogenic response. Whether these IL-10- producing cells are from the 'natural' Treg population that expresses the forkhead box p3 (Foxp3) transcription factor is less clear, and often they are not. We discuss some recent studies that might provide insight into how best to expand these protective T cells and highlight some outstanding issues requiring further investigation.
Leech
M
M
University of Edinburgh, Institute of Immunology and Infection Research, School of Biological Sciences, Edinburgh, UK.
Anderton
S
S
D000485:Allergens / Q000627:therapeutic use; D000818:Animals; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation; D003888:Desensitization, Immunologic / Q000639:trends; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016219:Immunotherapy, Adoptive / Q000639:trends*; D008213:Lymphocyte Activation; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014611:Vaccination / Q000639:trends
D000485:Allergens; D001324:Autoantigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors