Regulatory T cells in B‐cell‐deficient and wild‐type mice differ functionally and in expression of cell surface markers

NOD.H-2h4 Mice

“…Resistance of B À/À mice to SAT is due, at least in part, to the activity of Treg, because transient depletion of Treg using either anti-CD25 in B À/À NOD.H-2h4 mice or diphtheria toxin in B À/À Foxp3DTR NOD.H-2h4 mice results in development of SAT (Ellis & Braley-Mullen, 2014;Yu, Maiti, et al, 2006), and BÀ/ÀCD28À/À mice that have ineffective Treg develop SAT (Ellis, Hong, et al, 2013). These studies indicate that Treg have an important role in inhibiting SAT when B cells are reduced or absent.…”

“…We believe that FO B cells are the primary effector and antigen-presenting cells in SAT, based on their upregulation of MHC class II during disease development, their presence in thyroid infiltrates and the fact that anti-CD20, which has relatively little effect on MZ B cells in adult NOD.H-2h4 mice, but depletes most FO B cells (Yu, Dunn, et al, 2008;Yu et al, 2012), can be administered to mice with established SAT, depleting B cells in the thyroid and greatly reducing SAT severity scores (Hong & Braley-Mullen, 2014). B cells also have an important, but as yet poorly defined, role in controlling Treg function (Ellis & Braley-Mullen, 2014). B cells also function as regulatory cells in some models (Lund & Randall, 2010) and one report suggests that B cells can have a regulatory function in SAT (Shi et al, 2014).…”

“…Foxp3GFP mice are useful for isolation, sorting, and tracking of Treg both in situ and in cell transfer experiments (Ellis, Hong, et al, 2013;Yu et al, 2012), and the Foxp3 DTR mice provide a means to transiently deplete Foxp3+ Treg without using anti-CD25 which can potentially have effects on effector T cells (Ellis & Braley-Mullen, 2014). These mice were used to demonstrate that Treg in BÀ/À NOD.H-2h4 mice are functionally superior to those in WT NOD.H-2h4 mice in their ability to suppress SAT (Ellis & Braley-Mullen, 2014). Treg in WT and B À/À mice also differ in expression of several cell surface markers, although it is not known if these phenotypic differences contribute to the functional differences (Ellis & BraleyMullen, 2014).…”

“…Our studies using the Foxp3 GFP and Foxp3 DTR mutants also demonstrate that after transient Treg depletion of BÀ/À mice using either anti-CD25 or administration of DT (in Foxp3DTR mice), the repopulating Treg differ both functionally and phenotypically from those present in unmanipulated BÀ/À mice. Treg that repopulate B À/À mice after depletion can no longer inhibit SAT development and their phenotype is like that of WT mice that have B cells (Ellis & Braley-Mullen, 2014).…”

“…Treg depletion of Foxp3 DTR WT and B À/À NOD.H-2h4 mice depletes peripheral Foxp3+ Treg for a very short time, i.e., after administration of DT, splenic Treg return to near normal numbers 6-7 days later (Ellis & Braley-Mullen, 2014). The Foxp3DTR mice therefore provide a useful model to determine when and for how long Treg have to be depleted in order to influence SAT severity.…”