title: T cell-intrinsic S1PR1 regulates endogenous effector T-cell egress dynamics from lymph nodes during infection.
abstract: Viral clearance requires effector T-cell egress from the draining lymph node (dLN). The mechanisms that regulate the complex process of effector T-cell egress from the dLN after infection are poorly understood. Here, we visualized endogenous pathogen-specific effector T-cell migration within, and from, the dLN. We used an inducible mouse model with a temporally disrupted sphingosine-1-phosphate receptor-1 (S1PR1) gene specifically in endogenous effector T cells. Early after infection, WT and S1PR1(-/-) effector T cells localized exclusively within the paracortex. This localization in the paracortex by CD8 T cells was followed by intranodal migration by both WT and S1PR1(-/-) T cells to positions adjacent to both cortical and medullary lymphatic sinuses where the T cells exhibited intense probing behavior. However, in contrast to WT, S1PR1(-/-) effector T cells failed to enter the sinuses. We demonstrate that, even when LN retention signals such as CC chemokine receptor 7 (CCR7) are down-regulated, T cell intrinsic S1PR1 is the master regulator of effector T-cell emigration from the dLN.
authors: Department of Immunology, University of Connecticut Health, Farmington, CT 06030; Centre d'Immunologie et des Maladies Infectieuses de Paris, UMR-S CR7, Université Pierre-et-Marie-Curie, University of Paris 6, Sorbonne Universités, F-75005 Paris, France; Centre d'Immunologie et des Maladies Infectieuses de Paris, UMR S 1135, INSERM, F-75005 Paris, France;
authors: Alexandre P
authors: AP
authors: Benechet
authors: Department of Immunology, University of Connecticut Health, Farmington, CT 06030;
authors: Manisha
authors: M
authors: Menon
authors: Department of Immunology, University of Connecticut Health, Farmington, CT 06030;
authors: Daqi
authors: D
authors: Xu
authors: Department of Immunology, University of Connecticut Health, Farmington, CT 06030;
authors: Tasleem
authors: T
authors: Samji
authors: Department of Immunology, University of Connecticut Health, Farmington, CT 06030;
authors: Leigh
authors: L
authors: Maher
authors: The Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114; Harvard Medical School, Boston, MA 02115;
authors: Thomas T
authors: TT
authors: Murooka
authors: The Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114; Harvard Medical School, Boston, MA 02115;
authors: Thorsten R
authors: TR
authors: Mempel
authors: Department of Immunology, University of Connecticut Health, Farmington, CT 06030;
authors: Brian S
authors: BS
authors: Sheridan
authors: Centre d'Immunologie et des Maladies Infectieuses de Paris, UMR-S CR7, Université Pierre-et-Marie-Curie, University of Paris 6, Sorbonne Universités, F-75005 Paris, France; Centre d'Immunologie et des Maladies Infectieuses de Paris, UMR S 1135, INSERM, F-75005 Paris, France;
authors: Francois M
authors: FM
authors: Lemoine
authors: Department of Immunology, University of Connecticut Health, Farmington, CT 06030; Department of Pediatrics, University of Connecticut Health, Farmington, CT 06030 kkhanna@uchc.edu.
authors: Kamal M
authors: KM
authors: Khanna
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D007239:Infections / Q000276:immunology* / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D049349:Receptors, Lysosphingolipid / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000081025:Sphingosine-1-Phosphate Receptors; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D054243:Vesicular Stomatitis / Q000276:immunology / Q000473:pathology; D014721:Vesicular stomatitis Indiana virus
chemical_list: D049349:Receptors, Lysosphingolipid; C556330:S1pr1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors
keywords: T-cell activation; T-cell migration; infection; sphingosine phosphate receptor-1