Dr. Thomas Luft, MD, PhD

© dkfz.de

One of the key problems of transplantational medicine is how to predict the direction of a immune response: Which measurable clinical parameters predict/anticipate the course of a graft rejection, an episode of Graft-versus-Host-Disease (GvHD) or of a severe infection?

Adaptive systems such as the immune system react to a variety of activation stimuli with an adjusted response, that minimally impacts the host while damaging the invading pathogens as intensely as necessary. During this process, cellular functions such as secretion of cytokines, migration, expression of surface proteins, and apoptosis are independently regulated.

The scientific focus of our group is the investigation of such cellular adaptive immune responses. We established an in vitro model of human dendritic cell (DC) differentiation, and with its help we described the regulation of adaptive processes by strength and persistence of extracellular stimuli as well as by intracellular signal transduction pathways.

The results of our in vitro model form the basis for the investigation of adaptive immune responses in patients having received blood- or bone marrow stem cell transplantations (SCT). In particular, we are focussing on the pathophysiology of Graft-versus-Host-Disease (GvHD). GvHD is a clinical term describing a heterogenous group of diseases with autoimmune-like characteristics associated with SCT. These reactions may cause life-threatening complications; however, they may also be beneficial by mediating the curative success of a SCT (GvL, graft versus leukemia reaction). In order to better understand the beneficial and deleterious aspects of GvHD, our group has prospectively collected blood samples from patients following SCT. By examining materials from SCT-patients, we are currently identifying markers that distinguish polarized immune responses in vivo.