The Immunoregulation Group focuses its research on the immunology of allogeneic stem-cell transplantation (SCT) — a treatment option for patients with high-risk leukemia and lymphoma. Donor T cells, co-transplanted with the stem-cell graft, contribute to the efficacy of this treatment modality by eradicating patient hematopoiesis and thus also leukemic cells (Graft-versus-Leukemia effect, GVL). However, donor T cells can also attack solid organs of patients and thereby cause Graft-versus-Host Disease (GVHD), a severe and sometimes life-threatening transplant complication. The research group previously showed that the co-transplantation of Foxp3+ regulatory T cells (Tregs) with the stem-cell graft can prevent this complication in mouse models.

More recently, the group demonstrated that in vitro-expanded donor Tregs are also effective when administered therapeutically in ongoing acute GVHD (Riegel et al, Leukemia, 2020). These findings from experimental SCT models are currently tested in clinical phase-I/II studies exploring donor Tregs for the treatment of acute GVHD (EudraCT Number: 2012-002685-12) and chronic GVHD (EudraCT Number: 2016-003947-12).

Here is a selection of the most important publications from the last few years:

Dittmar DJ*, Pielmeier F*, Strieder N, Fischer A, Herbst M, Stanewsky H, Wenzl N, Röseler E, Eder R, Gebhard C, Schwarzfischer-Pfeilschifter L, Albrecht C, Herr W, Edinger M#, Hoffmann P#, Rehli M#. Donor regulatory T cells rapidly adapt to recipient tissues to control murine acute graft-versus-host disease. Nat Commun. 2024 Apr 15;15(1):3224. doi: 10.1038/s41467-024-47575-z. PMID: 38622133

Seefried M, Hundhausen N, Kroeger I, Büttner-Herold M, Hoffmann P, Edinger M, Ullrich E, Berberich-Siebelt F, Britt WJ, Mach M, Winkler TH. Murine cytomegalovirus reactivation concomitant with acute graft-versus-host disease is controlled by antibodies. JCI Insight. 2023 Mar 8;8(5):e149648. doi: 10.1172/jci.insight.149648. PMID: 36719764

Delacher M, Simon S, Sanderink L, Hotz-Wagenblatt A, Wuttke M, Schambeck K, Schmidleithner L, Bittner S, Pant A, Ritter U, Hehlgans T, Riegel D, Schneider V, Groeber-Becker FK, Eigenberger A, Gebhard C, Strieder N, Fischer A, Rehli R, Hoffmann P, Edinger M, Strowig T, Huehn J, Schmidl C, Werner JM, Prantl L, B Brors B, Imbusch CD, Feuerer M. Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells. Immunity 2021 Apr 13; 54(4):702-720.e17. doi: 10.1016/j.immuni.2021.03.007. PMID: 33789089

Riegel C, Boeld TJ, Doser K, Huber E, Hoffmann P*, Edinger M*. Efficient treatment of murine acute GvHD by in vitro expanded donor regulatory T cells. Leukemia 2020 Mar;34(3):895-908. doi: 10.1038/s41375-019-0625-3. PMID: 31719679

Delacher M, Imbusch C, Hotz-Wagenblatt A, Mallm JP, Bauer K, Simon M, Riegel D, Rendeiro AF, Bittner S, Sanderink L, Pant A, Schmidleithner L, Braband KL, Echtenachter B, Fischer A, Giunchiglia V, Hoffmann P, Edinger M, Bock C, Rehli M, Brors B, Schmidl C, Feuerer M. Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF. Immunity 2020 Feb 18;52(2):295-312.e11. doi: 10.1016/j.immuni.2019.12.002. PMID: 31924477

Hoffmann P, Boeld TJ, Eder R, Huehn J, Floess S, Wieczorek G, Olek S, Dietmaier M, Andreesen R, Edinger M. Loss of FOXP3 expression in natural human CD4+CD25+ regulatory T cells upon repetitive in vitro stimulation. Eur J Immunol 2009 Apr;39(4):1088-97. doi: 10.1002/eji.200838904. PMID: 19283780

Hoffmann P, Eder R, Boeld TJ, Doser K, Piseshka B, Andreesen R, Edinger M. Only the CD45RA+ subpopulation of CD4+CD25high T cells gives rise to homogeneous regulatory T cell lines upon in vitro expansion. Blood 2006 Dec;108(13):4260-7. doi: 10.1182/blood-2006-06-027409. PMID: 16917003

Merad M, Hoffmann P, Ranheim E, Slaymaker S, Manz MG, Lira SA, Charo I, Cook DN, Weissman IL, Strober S, Engleman EG. Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease. Nat Med 2004 May;10(5):510-7. doi: 10.1038/nm1038. PMID: 15098028

Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, Negrin RS. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med 2003 Sep;9(9):1144-50. doi: 10.1038/nm915. PMID: 12925844

Hoffmann P, Ermann J, Edinger M, Fathman CG, Strober S. Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med 2002 Aug 5;196(3):389-99. doi: 10.1084/jem.20020399. PMID: 12163567

The research group explores basic transplantation immunology in experimental in vivo models, characterizes alloresponses and their suppression using human immune cells, and performs immune monitoring studies using blood samples from transplanted patients. Furthermore, the group closely cooperates with the José-Carreras-Center in the development of novel cell therapy products and the conduction and immune monitoring of clinical trials.