Imaging Human Immune Cell Infiltration in a Xenograft Graft-Versus-Host Disease Model

Graft versus host disease (GvHD) is one of the major complications of hematopoetic stem cell transplantation (HSCT), and is characterized by massive alloreactive T cell infiltration into target organs and tissues. Currently, non-invasive tools to diagnose and follow up disease are lacking. Here we show non-invasive imaging of infiltrating immunocytes in a human xenograft model for chronic GvHD, using a single domain camelid-derived antibody fragment (VHH) specific for human Class II MHC products present on myeloid cells, B cells and activated T cells. NSG (NOD-scid gamma) mice reconstituted with human fetal thymus, bone marrow and liver (BLT mice) spontaneously develop a GvHD-like condition, characterized by alopecia, blepharitis and target organ infiltration by activated human T cells. In diseased animals, we show an increased PET signal in the liver, attributable to infiltration of activated Class II MHC positive T cells. Non-invasive imaging of specific immune infiltration and activation could thus be of importance for diagnosis and treatment evaluation of GvHD and holds promise for other diseases characterized by inflammation.