Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1321-1332 |
| Number of pages | 12 |
| Journal | Journal of Experimental Medicine |
| Volume | 207 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 7 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis. / Feng, Ting; Wang, Lanfang; Schoeb, Trenton R.; Elson, Charles O.; Cong, Yingzi.
In: Journal of Experimental Medicine, Vol. 207, No. 6, 07.06.2010, p. 1321-1332.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis
AU - Feng, Ting
AU - Wang, Lanfang
AU - Schoeb, Trenton R.
AU - Elson, Charles O.
AU - Cong, Yingzi
PY - 2010/6/7
Y1 - 2010/6/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77953486362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953486362&partnerID=8YFLogxK
U2 - 10.1084/jem.20092253
DO - 10.1084/jem.20092253
M3 - Article
C2 - 20498021
AN - SCOPUS:77953486362
VL - 207
SP - 1321
EP - 1332
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 6
ER -