Skip to Main content Skip to Navigation
Journal articles

CD4CD8aa Lymphocytes, A Novel Human Regulatory T Cell Subset Induced by Colonic Bacteria and Deficient in Patients with Inflammatory Bowel Disease

Abstract : How the microbiota affects health and disease is a crucial question. In mice, gut Clostridium bacteria are potent inducers of colonic interleukin (IL)-10-producing Foxp3 regulatory T cells (Treg), which play key roles in the prevention of colitis and in systemic immunity. In humans, although gut microbiota dysbiosis is associated with immune disorders, the underlying mechanism remains unknown. In contrast with mice, the contribution of Foxp3 Treg in colitis prevention has been questioned, suggesting that other compensatory regulatory cells or mechanisms may exist. Here we addressed the regulatory role of the CD4CD8 T cells whose presence had been reported in the intestinal mucosa and blood. Using colonic lamina propria lymphocytes (LPL) and peripheral blood lymphocytes (PBL) from healthy individuals, and those with colon cancer and irritable bowel disease (IBD), we demonstrated that CD4CD8aa (DP8a) T lymphocytes expressed most of the regulatory markers and functions of Foxp3 Treg and secreted IL-10. Strikingly, DP8a LPL and PBL exhibited a highly skewed repertoire toward the recognition of Faecalibacterium prausnitzii, a major Clostridium species of the human gut microbiota, which is decreased in patients with IBD. Furthermore, the frequencies of DP8a PBL and colonic LPL were lower in patients with IBD than in healthy donors and in the healthy mucosa of patients with colon cancer, respectively. Moreover, PBL and LPL from most patients with active IBD failed to respond to F. prausnitzii in contrast to PBL and LPL from patients in remission and/or healthy donors. These data (i) uncover a Clostridium-specific IL-10-secreting Treg subset present in the human colonic LP and blood, (ii) identify F. prausnitzii as a major inducer of these Treg, (iii) argue that these cells contribute to the control or prevention of colitis, opening new diagnostic and therapeutic strategies for IBD, and (iv) provide new tools to address the systemic impact of both these Treg and the intestinal microbiota on the human immune homeostasis.
Document type :
Journal articles
Complete list of metadatas

Cited literature [40 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01280941
Contributor : Elizabeth Bernardo <>
Submitted on : Tuesday, March 1, 2016 - 2:12:31 PM
Last modification on : Thursday, August 20, 2020 - 3:05:18 AM
Long-term archiving on: : Thursday, June 2, 2016 - 10:54:23 AM

File

Sarrabayrouse et al 2015.pdf
Publication funded by an institution

Identifiers

Citation

Guillaume Sarrabayrouse, Céline Bossard, Joe-Marc Chauvin, Anne Jarry, Guillaume Meurette, et al.. CD4CD8aa Lymphocytes, A Novel Human Regulatory T Cell Subset Induced by Colonic Bacteria and Deficient in Patients with Inflammatory Bowel Disease. PLoS Biology, Public Library of Science, 2014, 12 (4), pp.e1001833. ⟨10.1371/journal.pbio.1001833⟩. ⟨inserm-01280941⟩

Share

Metrics

Record views

570

Files downloads

484