Regulatory T cells in B cell-deficient mice differ from those in WT mice in function and expression of cell surface markers (BA13P.119)

Abstract

Abstract 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 unless Treg are transiently depleted. To determine if Treg from WT and B-/- mice differ in their ability to suppress effectors from a single source, splenocytes from CD28-/-B-/- mice (effector cells and APC) were cultured with or without sorted Treg from Foxp3-GFP WT or B-/- mice before transfer to mice lacking T cells. Recipients of Treg from B-/- mice had significantly lower SAT severity scores compared to those given Treg from WT mice, indicating that Treg in B-/- and WT mice differ functionally. Treg from WT and B-/- mice also differ in expression of TNF receptor superfamily members CD27, TNFR II p75, and GITR. After transient Treg depletion with anti-CD25 or diphtheria toxin, repopulating Treg in B-/- mice had reduced suppressor function, and expression of CD27, p75 and GITR was like that of WT Treg. If B cells were present during development of B-/- Treg in bone marrow chimeras or added to cultures of B-/- Treg and T effectors, expression of CD27, p75 and GITR by Treg from B-/- mice was comparable to that of WT Treg, and suppressive function was reduced. These results establish for the first time that Treg in WT and B-/- mice differ both functionally and phenotypically, and both are altered when B cells are present during Treg development and during interaction of Treg with T effectors.