Single cell analysis shows decreasing FoxP3 and TGFβ1 coexpressing CD4+CD25+ regulatory T cells during autoimmune diabetes

SM Pop, CP Wong, DA Culton, SH Clarke… - The Journal of …, 2005 - rupress.org
SM Pop, CP Wong, DA Culton, SH Clarke, R Tisch
The Journal of experimental medicine, 2005rupress.org
Natural CD4+ CD25+ regulatory T (CD4+ CD25+ T reg) cells play a key role in the
immunoregulation of autoimmunity. However, little is known about the interactions between
CD4+ CD25+ T reg cells and autoreactive T cells. This is due, in part, to the difficulty of using
cell surface markers to identify CD4+ CD25+ T reg cells accurately. Using a novel real-time
PCR assay, mRNA copy number of FoxP3, TGFβ1, and interleukin (IL)-10 was measured in
single cells to characterize and quantify CD4+ CD25+ T reg cells in the nonobese diabetic …
Natural CD4+CD25+ regulatory T (CD4+CD25+ T reg) cells play a key role in the immunoregulation of autoimmunity. However, little is known about the interactions between CD4+CD25+ T reg cells and autoreactive T cells. This is due, in part, to the difficulty of using cell surface markers to identify CD4+CD25+ T reg cells accurately. Using a novel real-time PCR assay, mRNA copy number of FoxP3, TGFβ1, and interleukin (IL)-10 was measured in single cells to characterize and quantify CD4+CD25+ T reg cells in the nonobese diabetic (NOD) mouse, a murine model for type 1 diabetes (T1D). The suppressor function of CD4+CD25+CD62Lhi T cells, mediated by TGFβ, declined in an age-dependent manner. This loss of function coincided with a temporal decrease in the percentage of FoxP3 and TGFβ1 coexpressing T cells within pancreatic lymph node and islet infiltrating CD4+CD25+CD62Lhi T cells, and was detected in female NOD mice but not in NOD male mice, or NOR or C57BL/6 female mice. These results demonstrate that the majority of FoxP3-positive CD4+CD25+ T reg cells in NOD mice express TGFβ1 but not IL-10, and that a defect in the maintenance and/or expansion of this pool of immunoregulatory effectors is associated with the progression of T1D.
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