title: Progression of armed CTL from draining lymph node to spleen shortly after localized infection with herpes simplex virus 1.
abstract: We have examined the generation of CTL immunity immediately after localized footpad infection with herpes simplex virus 1 (HSV-1) using three coordinated in vivo T cell tracking methodologies. Tetrameric MHC class I containing the immunodominant peptide from HSV-1 glycoprotein B (gB) showed that after infection the proportion of Ag-specific T cells peaked at day 5 within draining popliteal lymph nodes and 2 days later in the spleen. Preferential expression of the activation marker CD25 by tetramer-positive cells in draining popliteal nodes but not spleen suggested that gB-specific T cells were initially activated within the lymph node. In vivo cytotoxicity assays showed that Ag-specific effector cells were present within the draining lymph nodes as early as day 2 after infection, with a further 2-day lag before detection in the spleen. Consistent with the very early arming of effector CTL in the draining lymph node, adoptive transfer of CFSE-labeled gB-specific transgenic T cells showed that they had undergone one to four rounds of cell division by day 2 after infection. In contrast, proliferating T cells were first detected in appreciable numbers in the spleen on day 4, at which time they had undergone extensive cell division. These data demonstrate that HSV-1-specific T cells are rapidly activated and armed within draining lymph nodes shortly after localized HSV-1 infection. This is followed by their dissemination to other compartments such as the spleen, where they further proliferate in an Ag-independent fashion.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Coles
authors.forename: Scott N
authors.initials: SN
authors.lastname: Mueller
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
mesh_terms: D000818:Animals; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000032:analysis; D006561:Herpes Simplex / Q000276:immunology* / Q000473:pathology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006614:Hindlimb; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus