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Wednesday, 7 October 2015

1916 Oct 3 James Herriot, Yorkshire veterinarian and author of All Creatures Great and Small.

International Immunopharmacology
Volume 11, Issue 5, May 2011, Pages 576–588
China Regulatory T Cells and Th17 2010 Conference

All creatures great and small: regulatory T cells in mice, humans, dogs and other domestic animal species


doi:10.1016/j.intimp.2010.11.003
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Abstract

Abnormalities of peripheral tolerance are thought to contribute to the pathogenesis of a number of inflammatory, autoimmune and neoplastic diseases of both humans and animals. Furthermore, the induction of allograft tolerance is the ‘holy grail’ of clinical transplantation. Of the various mechanisms underlying peripheral tolerance, regulatory T cells (Tregs) have risen to particular prominence. Various Treg subsets have been characterised, including naturally occurring cells that develop along a regulatory lineage in the thymus and induced cells that arise in the periphery from conventional T cell precursors. The transcription factor Forkhead box (Foxp3) serves a crucial role in stabilising the Treg transcriptome and is a faithful marker of peripheral Tregs in the mouse, though its expression is somewhat more promiscuous in man. Regulatory T cells display a wide spectrum of suppressive and cytotoxic mechanisms and may convert to specific T helper cell subsets in response to appropriate inflammatory cues. Although knowledge of Tregs in domestic animal species is still in its infancy, a growing body of literature is accumulating in the dog, cat, pig, cow, sheep and horse. We highlight our own and other studies of Tregs in the dog, an important veterinary species and a model for a number of human diseases. The ethos of ‘One Health, One Medicine’ is anticipated to accelerate efforts to close the knowledge gap between domestic animal and mainstream species in this field. We predict that the prodigious pace of research into Tregs will continue unabated for years to come, fuelled by the exciting therapeutic potential of these cells.

Abbreviations

  • APC, antigen-presenting cell;
  • CTLA-4, cytotoxic T lymphocyte antigen-4;
  • Tcon, conventional (i.e. non-regulatory) T cell;
  • DC, dendritic cell;
  • IDO, indoleamine dioxygenase;
  • LFA-1, leukocyte function antigen-1;
  • ICAM-1, intercellular adhesion molecule-1;
  • LAG-3, lymphocyte activation gene-3;
  • FGL-2, fibrinogen-like protein-2;
  • LAP, latency activation peptide;
  • ThGC, germinal centre helper T cell (most authors have favoured the term TFH — follicular B helper T cell whether these cells represent the same subset is unclear);
  • FasL, Fas ligand;
  • ICOS (CD278), inducible T cell co-stimulator;
  • Gz, granzyme;
  • DN, double negative (i.e. CD3+CD4−CD8−);
  • TRAIL, tumour necrosis factor-related apoptosis-inducing ligand;
  • DR5 (CD262), death receptor 5 or tumour necrosis factor receptor super family member 10b;
  • Bim, B cell chronic lymphocytic leukaemia/lymphoma 2 (Bcl-2)-interacting mediator of cell death;
  • pDC, plasmacytoid dendritic cell;
  • mTOR, molecular target of rapamycin;
  • ILT3/ILT4, immunoglobulin-like transcript 3/4;
  • ATP, adenosine triphosphate;
  • AMP, adenosine monophosphate;
  • COX-2, cyclo-oxygenase-2;
  • PGE2, prostaglandin E2

Keywords

  • Regulatory T cell;
  • Foxp3/FOXP3;
  • Dog;
  • Veterinary;
  • Functional mechanisms;
  • Immunotherapy

Corresponding author. Tel.: +44 20 7468 1222, +44 7940 812188; fax: +44 20 7468 5204.
Copyright © 2010 Elsevier B.V. All rights reserved.
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