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. Methods to explore the dynamics of immune responses are needed to elucidate their role in such conditions. Immuno-PET is a non-invasive method to simultaneously explore disease and immune cell infiltration. NOD-SCID mice reconstituted with human fetal thymus, bone marrow and liver (BLT mice) spontaneously develop a GvHD-like condition. We developed a labeling strategy to install PET radioisotopes onto a single domain camelid-derived antibody fragment specific for human Class II MHC products, present on myeloid cells, B cells and activated T cells, to non-invasively monitor infiltrating immunocytes in this human xenograft model for chronic GvHD. 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 immune infiltration and activation could thus be of importance for diagnosis and evaluation of treatment of GvHD and holds promise for other diseases characterized by inflammation.

Noninvasive imaging of human immune cell infiltration in a human xenograft model of graft-versus-host disease

254th National Meeting (2017)

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