Staff: Dr. Simon Völkl (Leiter), Tabea Haug (Naturwissenschaftliche Doktorandin), Dorothea Gebhardt (MTA), Florentine Koppitz (MTA), Jana Berger (MTA)
Regulatory T cells (Treg) play an important role in the maintenance of immune tolerance to self antigens and are involved in modulating immune responses to promote resolution of inflammation. Recently, a novel subset of TCRαβ+ CD4- CD8- double-negative T (DNT) cells has been described to suppress immune responses in both mice and humans. Moreover, in murine models infusion and/or activation of DN T cells specifically suppressed alloreactive T cells and prevented development of Graft-versus-Host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Our lab has demonstrated that human DNT cells like their murine counterparts are highly potent suppressor cells of both, CD4+ and CD8+ T-cell responses. Currently, we are interested in the exact mechanisms of human DNT-cell mediated suppression. Moreover, we investigate whether human DNT cells offer an in vivo regulatory function and affect GvHD in patients after HSCT. Further understanding of the mechanisms involved in human DNT-cell suppression may have important implications for treatment of acute and/or chronic inflammatory graft-versus-host reactions.
As further project we investigate the importance of human DNT cells in autoimmune diseases. We are especially interested in studying a rare human disorder of dysregulated lymphocyte apoptosis, called Autoimmune Lymphoproliferative Syndrome (ALPS). This disease is characterized by a highly elevated frequency of circulating DNT cells. By now, the origin and functionality of this uncommon cell subpopulation still remain elusive. We are interested in the mechanisms leading to the accumulation of DNT cells and the functional properties of these cells. Moreover, we want to determine whether DNT cells facilitate the pathogenesis of ALPS.
Völkl S, Rensing-Ehl A, Allgäuer A, Schreiner E, Lorenz MR, Rohr J, Klemann C, Fuchs I, Schuster V, von Bueren AO, Naumann-Bartsch N, Gambinerie E, Siepermann K, Kobbe R, Nathrath M, Arkwright PD, Miano M, Stachel KD, Metzler M, Schwarz K, Kremer AN, Speckmann C, Ehl S, Mackensen A. Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome. Blood 2016, 128(2):227-38
Comment on Völkl et al: Carl E. Allen. ALPS DNT cells: active senior living with mTOR. Blood 2016, 128(2):152
Allgäuer A, Schreiner E, Ferrazzi F, Ekici AB, Gerbitz A, Mackensen A, Völkl S. IL-7 abrogates the immunosuppressive function of human double-negative T cells by activating Akt/mTOR signaling. Journal of Immunology 2015, 195(7):3139-48
Rensing-Ehl A, Völkl S, Speckmann C, Lorenz MR, Ritter J, Janda A, Abinun M, Pircher HP, Bengsch B, Thimme R, Fuchs I, Ammann S, Allgäuer A, Kentouche K, Cant A, Hambleton S, Bettoni da Cunha C, Huetker S, Kühnle I, Pekrun A, Seidel MG, Hummel M, Mackensen A, Schwarz K, Ehl S. Abnormally differentiated CD4+ or CD8+ T-cells with phenotypic and genetic features of double negative T-cells in human Fas deficiency. Blood 2014, 124(6):851-60