| First Author | Feng T | Year | 2010 |
| Journal | J Exp Med | Volume | 207 |
| Issue | 6 | Pages | 1321-32 |
| PubMed ID | 20498021 | Mgi Jnum | J:338008 |
| Mgi Id | MGI:6203789 | Doi | 10.1084/jem.20092253 |
| Citation | Feng T, et al. (2010) Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis. J Exp Med 207(6):1321-32 |
| abstractText | Little is known about how the microbiota regulates T cell proliferation and whether spontaneous T cell proliferation is involved in the pathogenesis of inflammatory bowel disease. In this study, we show that stimulation of innate pathways by microbiota-derived ligands and antigen-specific T cell stimulation are both required for intestinal inflammation. Microbiota-derived ligands promoted spontaneous T cell proliferation by activating dendritic cells (DCs) to produce IL-6 via Myd88, as shown by the spontaneous proliferation of T cells adoptively transferred into specific pathogen-free (SPF) RAG-/- mice, but not in germfree RAG-/- mice. Reconstitution of germfree RAG-/- mice with cecal bacterial lysate-pulsed DCs, but not with IL-6-/- or Myd88-/- DCs, restored spontaneous T cell proliferation. CBir1 TCR transgenic (CBir1 Tg) T cells, which are specific for an immunodominant microbiota antigen, induced colitis in SPF RAG-/- mice. Blocking the spontaneous proliferation of CBir1 Tg T cells by co-transferring bulk OT II CD4+ T cells abrogated colitis development. Although transferred OT II T cells underwent spontaneous proliferation in RAG-/- mice, the recipients failed to develop colitis because of the lack of cognate antigen in the intestinal lumen. Collectively, our data demonstrate that induction of colitis requires both spontaneous proliferation of T cells driven by microbiota-derived innate signals and antigen-specific T cell proliferation. |
