First Author | Nutsch K | Year | 2016 |
Journal | Cell Rep | Volume | 17 |
Issue | 1 | Pages | 206-220 |
PubMed ID | 27681432 | Mgi Jnum | J:240570 |
Mgi Id | MGI:5887174 | Doi | 10.1016/j.celrep.2016.08.092 |
Citation | Nutsch K, et al. (2016) Rapid and Efficient Generation of Regulatory T Cells to Commensal Antigens in the Periphery. Cell Rep 17(1):206-20 |
abstractText | Commensal bacteria shape the colonic regulatory T (Treg) cell population required for intestinal tolerance. However, little is known about this process. Here, we use the transfer of naive commensal-reactive transgenic T cells expressing colonic Treg T cell receptors (TCRs) to study peripheral Treg (pTreg) cell development in normal hosts. We found that T cells were activated primarily in the distal mesenteric lymph node. Treg cell induction was rapid, generating >40% Foxp3(+) cells 1 week after transfer. Contrary to prior reports, Foxp3(+) cells underwent the most cell divisions, demonstrating that pTreg cell generation can be the dominant outcome from naive T cell activation. Moreover, Notch2-dependent, but not Batf3-dependent, dendritic cells were involved in Treg cell selection. Finally, neither deletion of the conserved nucleotide sequence 1 (CNS1) region in Foxp3 nor blockade of TGF-beta (transforming growth factor-beta)-receptor signaling completely abrogated Foxp3 induction. Thus, these data show that pTreg cell selection to commensal bacteria is rapid, is robust, and may be specified by TGF-beta-independent signals. |