Abstracts (complete list) - Wissenschaft Online

Svetlana Karakhanova, Markus Schneider, Johannes Schenkel, Markus Munder
Steroids modulate the T effector cell / TREG / dendritic cell
balance during treatment of Graft-versus-Host Disease.
Allogeneic stem-cell transplantation (allo-SCT) is a potentially curative treatment for
various hematological malignancies. CD4+CD25++ regulatory T cells (TREG) regulate
immune responses and Graft-versus Host Disease (GvHD) after allo-SCT. We have
shown that the initial phase of GvHD correlates with a significant reduction of TREG in
the peripheral blood, while at later stages and especially during intensified
immunosuppressive therapy with steroids increased numbers of TREG appear in the
peripheral blood. We also found a change in phenotype of highly purified, in vitro
expanded CD4+CD25++ cells of patients during steroid medication. In contrast to
expanded TREG from healthy donors or GvHD patients without steroid medication, CD4
+CD25++ sorted cells from steroid-treated patients loose their TREG phenotype and
function in expansion cultures. During in vitro activation, steroids induce an increased
frequency of the CD4+CD25++ population in PBMC from healthy donors and lead to the
acquisition of a TREG like phenotype in CD4+CD25- T cells. Also, CD4+CD25++ cells
are less sensitive to steroid-induced cell death in comparison with conventional T cells.
Finally, dexamethason treatment of different dendritic cell populations leads to the
blockade of cytokine-induced maturation and consecutively to an impaired ability of the
dendritic cells to prime immune responses in CD4+ cells. Our findings suggest that
steroids can influence three major compartments of the immune response (T effector
cells, TREG cells and dendritic cells) simultaneously. This has implications for the
steroid-based treatment of GvHD after SCT.