Cognate antigen engagement on parenchymal cells stimulates CD8+ T cell proliferation in situ

• Published in: Nature communications 2017-04, Vol.8 (1), p.14809-14809, Article 14809
• Main Authors: Sutherland, Robyn M., Londrigan, Sarah L., Brady, Jamie L., Carrington, Emma M., Marchingo, Julia M., Heinzel, Susanne, Hodgkin, Philip D., Graham, Kate L., Kay, Thomas W., Zhan, Yifan, Lew, Andrew M.
• Format: Article
• Language: English
• Subjects: 631/250/21/1293; 631/250/2152/1566/20; Animals; Antigen presentation; Antigen Presentation - immunology; Antigens - immunology; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cell growth; Cell Proliferation; Female; Humanities and Social Sciences; Immunology; Inflammation - immunology; Interleukin-2 - metabolism; Islets of Langerhans - cytology; Islets of Langerhans - immunology; Lymph Nodes - immunology; Lymphocytes; Male; Mice; Mice, Transgenic; Models, Biological; multidisciplinary; Ovalbumin - immunology; Parenchymal Tissue - cytology; Parenchymal Tissue - immunology; Peptides; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms14809

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. Professional antigen presenting cells (APC) are the major activator of T cells that then hone to sites of inflammation. Using islet cell grafts, here the authors show that parenchymal cells can present antigen to activate CD8 + T cells at inflammatory sites, coining this a ‘mezzanine response’ distinct from primary and secondary responses associated with professional APCs.