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Publication : Complementary role of CD4+CD25+ regulatory T cells and TGF-beta in oral tolerance.

First Author  Chung Y Year  2005
Journal  J Leukoc Biol Volume  77
Issue  6 Pages  906-13
PubMed ID  15758078 Mgi Jnum  J:98607
Mgi Id  MGI:3579204 Doi  10.1189/jlb.1004599
Citation  Chung Y, et al. (2005) Complementary role of CD4+CD25+ regulatory T cells and TGF-{beta} in oral tolerance. J Leukoc Biol 77(6):906-13
abstractText  CD4(+)CD25(+) regulatory T cells are thought to be generated in the periphery as well as in the thymus. We sought to determine the roles played by CD4(+)CD25(+) T cells and transforming growth factor-beta (TGF-beta) in the induction and maintenance of tolerance generated by oral antigens in BALB/c mice. We found that oral administration of a high dose of ovalbumin (OVA) suppressed OVA-specific proliferation and antibody production in BALB/c mice depleted of CD25(+) cells. In contrast, the unresponsiveness induced by lower doses of OVA was only partially blocked by CD25 depletion prior to feeding. Depletion of CD4(+)CD25(+) cells after mice were orally tolerized did not reverse the tolerant status, indicating that these cells were not required to maintain the established tolerance. Furthermore, the induction of oral tolerance was not hampered by the administration of TGF-beta-neutralizing antibodies. However, in mice depleted of CD25(+) cells, anti-TGF-beta-neutralizing antibodies blocked the induction of tolerance, regardless of whether the mice followed the high- or low-dose regimens of oral OVA. CD25 depletion together with TGF-beta neutralization led the expansion of OVA-specific CD4 T cells against the subsequent antigen challenge, and each treatment alone did not. Our findings indicate that CD4(+)CD25(+) T cells and TGF-beta play a complementary role in the induction of oral tolerance, at least in part, by regulating the expansion of antigen-specific CD4 T cells.
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