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Research Activities of the
Laboratory for Immunoregulation

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Department of Haematology and Oncology
University Hospital Regensburg
Franz-Josef-Strauss Allee 11
93042 Regensburg, Germany
Tel.: +49 (0)941 944 5557 (ME) or 5514 (PH)
Fax: +49 (0)941 944 5502
Lab Tel.: +49 (0)941 944 5546 or 5549
e-mail: first name.family name@klinik.uni-regensburg.de



Clinical Research Group KFO 146: http://www-kfo146.uni-regensburg.de/


Matthias Edinger, M.D.
Matthias Edinger, M.D.
Petra Hoffmann, Ph.D.
Petra Hoffmann, Ph.D.

PhD Students:

Tina Boeld
Julia Albrecht
Kristina Doser

Technical Assistents:
Ruediger Eder
Jasmin Stahl 

M.D. Students:
Biserka Piseshka
Peter Hamerlik

Research Field
Immunoregulation is an intrinsic part of the physiology of the immune system. The successful regulation and termination of an immune response is as important as its initiation in order to protect the organism from immune cell mediated tissue damage and autoimmune diseases. Soluble mediators, such as IL-4, IL-10 or TGF-b and specialized cell populations, such as immature dendritic cells, Th2 , Tr1 or NKT cells all contribute to this form of immunoregulation.

In our laboratory, we focus on the cellular components involved in this process, especially a subpopulation of CD4+ T cells that constitutively expresses CD25 (a-chain of the IL-2 receptor), in order to investigate their role in transplantation tolerance. CD4+CD25+ T cells differ from CD25- CD4 and CD8 T cells by their lack of proliferation and cytokine secretion in response to TCR-mediated stimuli (anergy). Although no specific surface marker for these cells is known so far, they can be identified by their selective expression of FOXP3, a member of the family of forkhead winged-helix transcription factors.

Peripheral blood CD4+ T cells
Peripheral blood CD4+ T cells

Furthermore, they suppress the proliferation of CD25- T cells in vitro and in vivo after polyclonal or allo-antigenic stimulation. Recently, we could show in murine models of allogeneic bone marrow transplantation (allo-BMT) that donor-derived CD4+CD25+ Treg cells suppress life threatening graft-versus-host disease (GVHD) after allogeneic BMT without necessarily abrogating the beneficial graft-versus-leukemia (GVL) effect.

Since both, GVHD and GVL effect are initiated by mature donor-derived T cells, we investigate possibilities to dissect beneficial (GVT) from harmful (GVHD) T cell effects by favouring natural mechanisms of immunosuppression. An improved understanding of the underlying biology might result in new strategies for the generation of tolerance after allogeneic BMT without loss of the beneficial GVT effects.
In our laboratory we address the following questions in murine model systems as well as in translational research on clinical samples and early clinical trials:

  • Pathophysiology of acute graft-versus-host disease in animal models
  • Role of donor CD4+CD25+ regulatory T cells in BMT and GVHD
  • Immune reconstitution after allogeneic BMT
  • Evaluation of human Treg cells in xenogenic GVHD
  • Characterization, isolation and in vitro expansion of human CD4+CD25+ regulatory T cells
  • Phase I clinical trial exploring the adoptive transfer of human Treg cells for prevention of GVHD
Phase I clinical trial: Patients with high disease relapse risk or minimal residual disease after allogeneic SCT are pre-emptively treated with donor lymphocytes after cessation of immunosuppressive GVHD prophylaxis. They receive up to 5 Mio CD4+CD25+ Treg cells per kg body weight isolated from their original stem cell donor, followed by conventional DLI after approximately 8-10 weeks.
Phase I clinical trial: Patients with high disease relapse risk or minimal residual disease after allogeneic SCT are pre-emptively treated with donor lymphocytes after cessation of immunosuppressive GVHD prophylaxis. They receive up to 5 Mio CD4+CD25+ Treg cells per kg body weight isolated from their original stem cell donor, followed by conventional DLI after approximately 8-10 weeks.

The group is supported by: Deutsche Forschungsgemeinschaft (German Research Society), Deutsche Krebshilfe (German Cancer Society), Wilhelm Sander-Stiftung, Jose Carreras Foundation, and the Regensburg Research Foundation (ReForM).  

Selected Publications  

  • Hoffmann, P., Eder, R., Boeld, T.J., Doser, K., Piseshka, B., Andreesen, R. and M. Edinger. Only the CD45RA+ subpopulation of CD4+CD25high T cells gives rise to homogeneous regulatory T cell lines upon in vitro expansion. Blood (prepublished online).
  • Greinix, HT, Socie, G., Bacigalupo, A., Holler, E., Edinger, M., Apperley, JF, Schwarz, T., Ullrich, SE, Albert, ML, Knobler, RM, Perritt, D and JLM Ferrara (2006). Assessing the potential role of photopheresis in hematopoietic stem cell transplant. Bone Marrow Transplant. 38(4):265-73.
  • Hoffmann, P., Boeld, T.J., Eder, R., Albrecht, K., Doser, K., Piseshka, B., Dada, A., Niemand, C., Assenmacher, M., Orso, E., Andreesen, R., Holler, E., Edinger, M. (2006). Isolation of CD4+CD25high regulatory T cells for clinical trials. .Biol Blood Marrow Transplant 12, 267-74
  • Hofffmann, P. & Edinger, M. (2006). CD4+CD25+ regulatory T cells and graft-versus-host disease. Semin Hematol, 43:62-69.
  • Hoffmann, P., Boeld, T.J., Piseshka, B, Edinger, M. (2005). Immunomodulation after allogeneic bone marrow transplantation by CD4+CD25+ regulatory T cells. Microbes Infect 7 (7-8): 1066-72.
  • Hoffmann, P, Ermann, J., Edinger, M. (2005). CD4+CD25+ regulatory T cells in allogeneic stem cell transplantation. Curr Top Microbiol Immunol. 293:265-85.
  • Ermann, J., Hoffmann, P., Edinger, M., Dutt, S., Higgins, J., Negrin, R.S., Fathman, C.G., Strober, S. (2005). Only the CD62L+ subpopulation of CD4+CD25+ regulatory T cells protects from lethal acute GVHD. Blood, 105: 2220-2226.
  • Verneris, M.R., Arshi, A., Edinger, M., Kornacker, M., Natkunam, Y., Karami, M., Cao, Y., Marina, N., Contag, C and R. Negrin (2005). Ewing’s family tumor cell lines express low levels of Her2/neu which can be used as a target to redirect ex vivo activated and expanded T cells. Clin Cancer Res. 11(12):4561-70.
  • Leemhuis, T., Wells, S., Scheffold, C., Edinger, M., Negrin, R. (2005). A phase I trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkins disease and non-Hodgkin lymphoma Biol Blood Marrow Transpl. 11:181-187.
  • Hoffmann, P., Eder, R., Kunz-Schughart, L.A., Andreesen, R., Edinger, M. (2004). Large scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells. Blood 104: 895-903.
  • Merad, M., P. Hoffmann, E. Ranheim, S. Slaymaker, M.G. Manz, S.A., Lira, I. Charo, D.N. Cook, I.L. Weissman, S. Strober, and E.G. Engleman (2004). Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft- versus-host disease. Nat.Med.10(5):510-17.
  • Mandl, S., Mari, C., Edinger, M., Negrin, R.S., Tait, J.F., Contag, C.H., Blankenberg, F (2004). In vivo dynamics of cell death in a mouse model of lymphoma: Multi-modality imaging identifies key imaging times for assessing response to chemotherapy. Mol. Imaging 3(1): 1-8
  • Edinger, M., Hoffmann, P., Ermann, J., Drago, K., Fathman, C.G., Strober, S., Negrin, R.S. (2003). CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus host disease after bone marrow transplantation. Nature Medicine, 9(9), 1144-50.
  • Edinger, M., Hoffmann, P., Contag, C.H., Negrin, R.S. (2003). Evaluation of effector cell fate and function by in vivo bioluminescence imaging. Methods, 31(2), 172-79.
  • Edinger, M., Cao, Y., Verneris, M.R., Bachmann, M.H., Contag, C.H., Negrin, R.S (2003). Revealing lymphoma growth and the efficacy of immune cell therapies using bioluminescence in vivo imaging. Blood 101(2), 640-8.
  • Mandl, S., Schimmelpfennig, C., Edinger, M., Negrin, R.S., Contag, C.H. (2003). Understanding immune cell trafficking patterns via in vivo bioluminescence imaging. J. Cell. Biochem., Suppl, 39: 239-248.
  • Hoffmann, P., Ermann, J., Edinger, M., Fathman, C.G., Strober, S. (2002). Donor type CD4+CD25+ T cells suppress lethal acute graft versus host disease after allogeneic bone marrow transplantation. J. Exp. Med. 196(3), 389-99.
  • Millan, M.T., J.A. Shizuru, P. Hoffmann, S. Dejbakhsh-Jones, J.D. Scandling, F.C. Grumet, J.C. Tan, O. Salvatierra, R.T. Hoppe, and S. Strober. (2002). Mixed chimerism and immunosuppressive drug withdrawal after HLA-mismatched kidney and hematopoietic progenitor transplantation. Transplantation 73:1386-1391.
  • Edinger, M., Cao, Y.A., Hornig, Y.S., Jenkins, D.E., Verneris, M.R., Bachmann, M.H., Negrin, R.S., Contag, C.H. (2002). Advancing animal models of neoplasia through in vivo bioluminescence imaging. Eur. J. Cancer 38(16), 2128-36.
  • Negrin, R.S., Edinger, M., Verneris, M., Cao, Y.A., Bachmann, M., Contag, C.H. (2002). Visualization of tumor growth and response to NK-T cell based immunotherapy using bioluminescence. Ann. Hematol. 81, Suppl. 2, 44-45.
  • Verneris, M.R., Baker, J., Edinger, M., Negrin, R.S. (2002). Studies of ex vivo activated and expanded CD8+ NK-T cells in humans and mice. J. Clin. Immunol. 22(3), 131-6.
  • Zeng, D., P. Hoffmann, F. Lan, P. Huie, J. Higgins, and S. Strober (2002). Unique patterns of surface receptors, cytokine secretion, and immune functions distinguish T cells in the bone marrow from those in the periphery: impact on allogeneic bone marrow transplantation. Blood 99:1449-1457.
  • Hardy, J., Edinger, M., Bachmann, M., Negrin, R.S., Fathman, G.C., Contag, C.H. (2001). Bioluminescence imaging of lymphocyte trafficking in vivo. Exp. Hematol. 29, 1353-1360.
  • Edinger, M., Sweeney, T.J., Tucker, A.A., Olomu, A.B., Negrin, R.S., Contag, C.H. (1999). Non-invasive assessment of tumor cell proliferation in animal models. Neoplasia 1: 303-310.

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Letzte Aktualisierung: 21.10.2008 | Online-Redaktion
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