Abstract
Intravital visualization of autoimmune-induced tissue damage and T
reg
cell protection shows contact-based immune cell interactions and growth of bystander tissue cells in pancreatic islet grafts.
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 (T
eff
) 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 (T
reg
) cells persistently contacted T
eff
cells with or without involvement of CD11c
+
dendritic cells, an observation conciliating with the in vitro “trademark” of T
reg
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.
