title: Limited Internodal Migration of T Follicular Helper Cells after Peripheral Infection with Herpes Simplex Virus-1.
abstract: The ability of CD4 T cells to give rise to specialized T follicular helper cells (TFH) critical to initiating appropriate Ab responses is regulated by environmental cues in lymphoid tissues draining the site of infection. In this study, we used a skin infection with HSV-1 characterized by the successive involvement of interconnected but distinct lymph nodes (LNs), to investigate the anatomical diversification of virus-specific CD4 T cell responses and the migratory capacity of TFH or their precursors. Whereas Th1 effector CD4 T cells expressing peripheral-targeting migration molecules readily migrated from primary to secondary reactive LNs, Bcl6(+) CXCR5(+) PD1(hi) TFH were largely retained at the site of initial activation with little spillover into the downstream LNs involved at later stages of infection. Consistent with this, TFH maintained high-level surface expression of CD69, indicative of impaired migratory capacity. Notably, the biased generation and retention of TFH in primary LNs correlated with a preferential generation of germinal centers at this site. Our results highlight a limited anatomical diversification of TFH responses and germinal center reactions that were imprinted within the first few cell divisions during TFH differentiation in LNs draining the site of initial infection.
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Sanda
authors.initials: S
authors.lastname: Stankovic
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Harpur
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Macleod
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Whitney
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia gebhardt@unimelb.edu.au agbrooks@unimelb.edu.au.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gebhardt
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria 3000, Australia gebhardt@unimelb.edu.au agbrooks@unimelb.edu.au.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D018858:Germinal Center / Q000276:immunology* / Q000473:pathology; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5 / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004268:DNA-Binding Proteins; D037181:Lectins, C-Type; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5; D000099192:CD69 Antigens; C490010:Bcl6 protein, mouse; C513179:CXCR5 protein, mouse