PURPOSE OF THE STUDY.
To determine if the gut microbiota is important for the development of regulatory T cells (TREG), which help maintain tolerance by regulating inflammatory responses in the intestine.
Studies were performed in mice.
The authors evaluated T-cell receptor (TCR) diversity and specificity of TREG and effector T cells isolated from the gut and peripheral lymphoid tissues. The authors then performed T-cell transfer studies to determine if lymphocytes specific for the gut microbiota had pathogenic potential in mice genetically predisposed for spontaneous colitis.
The authors discovered that the TCR repertoire for colonic TREG was distinct from that for other effector T cells in the gut and TREG isolated from other lymphoid tissues. A significant proportion of colonic TREG were specific for antigens derived from gut bacteria. Unlike conventional TREG, which are derived in the thymus, colonic TREG primarily developed from naïve T cells in peripheral tissue. The TCR repertoire of colonic TREG was shaped by the animal’s own unique microbiome, as TREG from one mouse did not recognize colonic bacteria from another mouse unless they were first co-housed. Finally, the authors demonstrated that in mice genetically predisposed for spontaneous colitis, naïve T cells could develop into pathogenic effector T cells rather than TREG.
In normal mice, T cells that recognize commensal bacteria preferentially differentiate into TREG in the colon, thereby promoting tolerance to the gut microbiota and preventing the development of detrimental inflammatory disease.
The gut microbiome has gained significant attention recently for its putative importance in human health and disease. In experimental animals, it has long been known that homeostasis critically depends on proper bidirectional communications between the microflora and the immune system. However, little is known about the specific mechanism or mechanisms by which an animal tolerates these trillions of microbes. The studies by Lathrop et al add direct evidence that each animal develops its own repertoire of peripherally induced TREG that are critically involved in promoting tolerance to foreign antigens in its gut. These findings also infer that alteration of the gut microbiota as seen with indiscriminate antibiotic use could disrupt the development of TREG, thereby predisposing individuals to developing immunopathology, such as inflammatory bowel disease or food allergies.
- Copyright © 2012 by the American Academy of Pediatrics