Real-time immune cell interactions in target tissue during autoimmune-induced damage and graft tolerance

• Published in: The Journal of experimental medicine Vol. 211; no. 3; pp. 441 - 456
• Main Authors: Miska, Jason, Abdulreda, Midhat H., Devarajan, Priyadharshini, Lui, Jen Bon, Suzuki, Jun, Pileggi, Antonello, Berggren, Per-Olof, Chen, Zhibin
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 10.03.2014
• Subjects: Adoptive Transfer; Analysis of Variance; Animals; Autoantigens - immunology; Autoimmunity - immunology; Bromodeoxyuridine; Cell Communication - immunology; Crosses, Genetic; Fluorescence; Image Processing, Computer-Assisted - methods; Islets of Langerhans Transplantation - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; RNA Interference; T-Lymphocytes, Regulatory - immunology; Transplantation Tolerance - immunology
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20130785

Real-time imaging studies are reshaping immunological paradigms, but a visual framework is lacking for self-antigen-specific T cells at the effector phase in target tissues. To address this issue, we conducted intravital, longitudinal imaging analyses of cellular behavior in nonlymphoid target tissues to illustrate some key aspects of T cell biology. We used mouse models of T cell–mediated damage and protection of pancreatic islet grafts. Both CD4+ and CD8+ effector T (Teff) lymphocytes directly engaged target cells. Strikingly, juxtaposed β cells lacking specific antigens were not subject to bystander destruction but grew substantially in days, likely by replication. In target tissue, Foxp3+ regulatory T (Treg) cells persistently contacted Teff cells with or without involvement of CD11c+ dendritic cells, an observation conciliating with the in vitro “trademark” of Treg function, contact-dependent suppression. This study illustrates tolerance induction by contact-based immune cell interaction in target tissues and highlights potentials of tissue regeneration under antigenic incognito in inflammatory settings.