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Center for Neurologic Diseases, Harvard Medical School, Boston, MA 02115
CD25+CD4+ T cells are naturally occurring
regulatory T cells that are anergic and have suppressive properties.
Although they can be isolated from the spleens of normal mice, there
are limited studies on how they can be activated or expanded in vivo.
We found that oral administration of OVA to OVA TCR transgenic mice
resulted in a modification of the ratio of
CD25+CD4+ to CD25-CD4+
cells with an increase of CD25+CD4+ T cells
accompanied by a decrease of CD25-CD4+ T
cells. The relative increase in CD25+CD4+ T
cells persisted for as long as 4 wk post feeding. We also found that
CTLA-4 was dominantly expressed in CD25+CD4+ T
cells and there was an increase in the percentage of
CD25+CD4+ T cells expressing CTLA-4 in OVA-fed
mice. In contrast to CD25-CD4+ cells,
CD25+CD4+ cells from fed mice proliferated only
minimally to OVA or anti-CD3 and secreted IL-10 and elevated levels
of TGF-
1 following anti-CD3 stimulation.
CD25+CD4+ cells from fed mice suppressed the
proliferation of CD25-CD4+ T cells in vitro
more potently than CD25+CD4+ T cells isolated
from unfed mice, and this suppression was partially reversible by IL-10
soluble receptor or TGF- soluble receptor and high concentration of
anti-CTLA-4. With anti-CD3 stimulation,
CD25+CD4+ cells from unfed mice secreted
IFN-
, whereas CD25+CD4+ cells from fed mice
did not. Adoptive transfer of CD25+CD4+ T cells
from fed mice suppressed in vivo delayed-type hypersensitivity
responses in BALB/c mice. These results demonstrate an Ag-specific in
vivo method to activate CD25+CD4+ regulatory T
cells and suggest that they may be involved in oral
tolerance.
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 T. L. Sumpter and D. S. Wilkes Role of autoimmunity in organ allograft rejection: a focus on immunity to type V collagen in the pathogenesis of lung transplant rejection Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1129 - L1139. [Abstract] [Full Text] [PDF]
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