Journal
JOURNAL OF IMMUNOLOGY
Volume 183, Issue 9, Pages 5477-5486Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0804267
Keywords
-
Categories
Funding
- INSERM
- Danone Research Center (Palaiseau, France)
- Association Francois Aupetit
Ask authors/readers for more resources
Evidence that CD4(+) regulatory T cells can control Ag-specific CD8(+) T cell-mediated colitis in immunocompetent mice is poorly documented. To examine the potential of CD4(+) T cells to control colitis, we used our model of CD8(+) T cell-mediated colitis induced by intracolonic sensitization followed by challenge with the hapten 2,4-dinitrobenzene sulfonic acid. The defect of CD4(+) T cells in MHC class II-deficient (A beta%) mice allowed priming of 2,4-dinitrobenzene sulfonic acid-specific IFN-gamma-producing CD8 colitogenic effectors and development of colitis in the otherwise resistant (-)C57BL/6 strain. Cotransfer experiments in RAG2% mice and ex vivo studies showed that CD4(+)CD25(+) T cells completely prevented CD8(+) T cell-mediated colitis and controlled CD8(+) T cell activation, respectively. In the susceptible BALB/c strain, Ab depletion revealed that lack of CD4(+) regulatory T cells resulted in 1) acute colitis elicited by a suboptimal dose of hapten challenge and 2) more severe relapsing episodes of colitis induced by effector/memory CD8(+) T cell-mediated colitis at an optimal dose of hapten challenge, even when CD4 depletion was performed just before the second challenge. Oral administration of the probiotic strain Lactobacillus casei DN-114001 alleviated colitis and increased the suppressive function of Foxp3(+) CD4(+) regulatory T cells of colon lamina propria. These data demonstrate that CD4(+) regulatory T cells exert a protective effect on colitis by controlling colitogenic effector/memory CD8(+) T cells during the effector (symptomatic) phase of acute and relapsing colitis, respectively. Probiotics with natural adjuvant effects on mucosal regulatory T cells may represent a valuable approach to alleviate the colitogenic effect of Tc1-type CD8(+) effectors. The Journal of Immunology, 2009, 183: 5477-5486.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available