title: Polyclonal Treg cells modulate T effector cell trafficking.
abstract: In this study, we have analyzed the in vivo dynamics of the interaction between polyclonal Foxp3(+)  Treg cells, effector T (Teff) cells, and DCs in order to further our understanding of the mechanisms of Treg cell-mediated suppression. Cotransfer of polyclonal activated Treg cells into healthy mice attenuated the induction of EAE. Suppression of disease strongly correlated with a reduced number of Teff cells in the spinal cord, but not with Treg cell-mediated inhibition of Th1/Th17 differentiation. Cotransfer of Treg cells with TCR-Tg Teff cells followed by immunization by multiple routes resulted in an enhanced number of Teff cells in the lymph nodes draining the site of immunization without an inhibition of Teff-cell differentiation. Fewer Teff cells could be detected in the blood in the presence of Treg cells and fewer T cells could access a site of antigen exposure in a modified delayed-type hypersensitivity assay. Teff cells recovered from LNs in the presence of Treg cells expressed decreased levels of CXCR4, syndecan, and the sphingosine phosphate receptor, S1P1 (sphingosine 1-phosphate receptor 1). Thus, polyclonal Treg cells influence Teff-cell responses by targeting trafficking pathways, thus allowing immunity to develop in lymphoid organs, but limiting the number of potentially auto-aggressive cells that are allowed to enter the tissues.
authors: Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Todd S
authors: TS
authors: Davidson
authors: Ethan M
authors: EM
authors: Shevach
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D049349:Receptors, Lysosphingolipid / Q000096:biosynthesis; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology; D053667:Syndecans / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism
chemical_list: C514936:CXCR4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D019718:Receptors, CXCR4; D049349:Receptors, Lysosphingolipid; D053667:Syndecans