title: Cognate antigen engagement on parenchymal cells stimulates CD8+T cell proliferation in situ.
abstract: T-cell responses are initiated upon cognate presentation by professional antigen presenting cells in lymphoid tissue. T cells then migrate to inflamed tissues, but further T-cell stimulation in these parenchymal target sites is not well understood. Here we show that T-cell expansion within inflamed tissues is a distinct phase that is neither a classical primary nor classical secondary response. This response, which we term 'the mezzanine response', commences within days after initial antigen encounter, unlike the secondary response that usually occurs weeks after priming. A further distinction of this response is that T-cell proliferation is driven by parenchymal cell antigen presentation, without requiring professional antigen presenting cells, but with increased dependence on IL-2. The mezzanine response might, therefore, be a new target for inhibiting T-cell responses in allograft rejection and autoimmunity or for enhancing T-cell responses in the context of microbial or tumour immunity.
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Sutherland
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Londrigan
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Brady
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Carrington
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Julia M
authors.identifier: 0000-0001-8823-9718
authors.initials: JM
authors.lastname: Marchingo
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Susanne
authors.identifier: 0000-0001-9524-2835
authors.initials: S
authors.lastname: Heinzel
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Hodgkin
authors.affiliation: St Vincent's Institute, Fitzroy, Victoria 3065, Australia.|Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria 3065, Australia.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Graham
authors.affiliation: St Vincent's Institute, Fitzroy, Victoria 3065, Australia.|Department of Medicine, St Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria 3065, Australia.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kay
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.|Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lew
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D007249:Inflammation / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010047:Ovalbumin / Q000276:immunology*; D000072356:Parenchymal Tissue / Q000166:cytology* / Q000276:immunology
chemical_list: D000941:Antigens; D007376:Interleukin-2; D010047:Ovalbumin