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

Abstract

Summary: NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) with chronic inflammation of thyroids by T and B cells. B-cell deficient (B-/-) mice are resistant to SAT but develop SAT if regulatory T (Treg) cells are transiently depleted. We established a transfer model using splenocytes from CD28-/- B-/- mice (effector cells and antigen-presenting cells) cultured with or without sorted Treg cells from Foxp3-GFP wild-type (WT) or B-/- mice. After transfer to mice lacking T cells, mice given Treg cells from B-/- mice had significantly lower SAT severity scores than mice given Treg cells from WT mice, indicating that Treg cells in B-/- mice are more effective suppressors of SAT than Treg cells in WT mice. Treg cells from B-/- mice differ from WT Treg cells in expression of CD27, tumour necrosis factor receptor (TNFR) II p75, and glucocorticoid-induced TNFR-related protein (GITR). After transient depletion using anti-CD25 or diphtheria toxin, the repopulating Treg cells in B-/- mice lack suppressor function, and expression of CD27, GITR and p75 is like that of WT Treg cells. If B-/- Treg cells develop with B cells in bone marrow chimeras, their phenotype is like that of WT Treg cells. Addition of B cells to cultures of B-/- Treg and T effector cells abrogates their suppressive function and their phenotype is like that of WT Treg cells. These results establish for the first time that Treg cells in WT and B-/- mice differ both functionally and in expression of particular cell surface markers. Both properties are altered after transient depletion and repopulation of B-/- Treg cells, and by the presence of B cells during Treg cell development or during interaction with effector T cells.