title: Regulatory T cells in B-cell-deficient and wild-type mice differ functionally and in expression of cell surface markers.
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 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.
authors.affiliation: Department of Medicine, University of Missouri, Columbia, MO, USA; Department of Molecular Microbiology & Immunology, University of Missouri, Columbia, MO, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Ellis
authors.forename: Helen
authors.initials: H
authors.lastname: Braley-Mullen
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D018106:CD28 Antigens / Q000172:deficiency / Q000235:genetics; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D019673:Genes, T-Cell Receptor alpha; D020022:Genetic Predisposition to Disease; D017493:Leukocyte Common Antigens / Q000235:genetics; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D010641:Phenotype; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D018183:Transplantation Chimera
chemical_list: D015415:Biomarkers; D018106:CD28 Antigens; D017493:Leukocyte Common Antigens
keywords: B cells; autoimmunity; regulatory T cell