Immunogenetics

Group Leader: Dr Dieter Kube

The group works on interleukin-10 (IL-10) in infectious diseases (Epstein-Barr-Virus associated malignancies and Plasmodium falciparum malaria) and aims to get a better understanding of the structure of the IL-10 gene and the role of the interleukin in host-parasite or host-virus interactions at the molecular level. Our strategy is to expand current
technological, investigative and diagnostic thresholds to a wide range of diseases, in order to provide new opportunities for intervention and treatment that are widely applicable. These include infectious diseases, cancer, acute and chronic inflammation and debilitating autoimmune conditions.

The immunogenetics group is led by Dr. Dieter Kube, who joined the department in 2002. Dieter Kube is a molecular biologist involved in cytokine and lymphoma research since 1992, immunogenetic studies since 1997 at the Universtiy of Cologne and work on Malaria since 1999 at the Eberhard-Karls University Tübingen. A main theme of the group is the Epstein-Barr virus (EBV) associated regulation of IL-10 in lymphomas. With his move to Göttingen the analysis of the deregulation of the Jak/STAT signaling pathway has become a central area of interest. The group comprises Diploma as well as Doctoral students in both medical and natural sciences. The group is currently involved in the investigation of the pathophysiology of malignant lymphomas using transcriptom and proteom- techniques such as cell culture systems, microsatellite multiplex analysis, reporter gene analysis (luciferase, GFP), nucleosome analysis, magnetic cell separation, cytokine expression profiling and signal transduction pathway analysis.

It currently has extensive collaborative projects with a number of laboratories in Belgium, France, Gabon, Germany, Italy, The Netherlands, USA, Scotland.

Dieter Kube is member of the editorial board of
Genes and Immunity.

Grants held

Deutsche Forschungsgemeinschaft (DFG)
Immunological analysis of Epstein-Barr-Virus positive malignant lymphoma (SFB502) (1997-1999) EBV-associated transcriptional regulation of IL-10 (Ku 954/4-1) (2000-2002) Haplotype dependent activation of IL-10 in infectious disease like Plasmodium falciparum Malaria"(Ku 954/5-1) (2000-2002) http://www.dfg.de/

DAAD
Analysis of cytokine expression of EBV-EBNA1 and EBV-LMP1 expressing lymphoma cells in mouse models (1997-1999) Analysis EBV-associated T-cell responses in Plasmodium falciparum infected children (2000-present) http://www.daad.de

1. Vockerodt M, Belge G, Kube D, Irsch J, Siebert R, Tesch H, Diehl V, Wolf J, Bullerdiek J, Staratschek-Jox A. An unbalanced translocation involving chromosome 14 is the probable cause for loss of potentially functional rearranged immunoglobulin heavy chain genes in the EBV positive Hodgkin's lymphoma derived cell line L591. British J Hematol. 2002, 119: 640-646

2. Kube D., Holtick U., Vockerodt M., Ahmadi T., Haier B., Behrmann I., Heinrich PC. Diehl V., Tesch H. STAT3 is constitutively activated in Hodgkin cell lines. Blood 2001, 98/3: 762-770

3. Vockerodt M., Haier B., Buttgereit P., Tesch H., and Kube D. The Epstein-Barr Virus Latent Membrane Protein 1 induces Interleukin-10 in Burkitts lymphoma cells but not in Hodgkins cells involving the p38/SAPK2 pathway. Virology, 2001, 280, 183-198

4. Kube D. & Vockerodt M. Transient gene expression and MACS enrichment. in Epstein Barr Virus Protocols. Ed. JB Wilson / GHW May, Humana Press; 2001 p155-165

5. Kube D., Schmidt D., Mörmann M., Uhlemann AC., Tomiuk J., Tesch H., Kremsner PG. Semiautomated and simultanious analysis of microsatellites by fluorescence based polymerase chain reaction in three loci of the interleukin-10 5Œ flanking region. Eur Cytokine Netw 2001 12/3:537-544

6. Kube D., Rieth H., Eskdale J., Kremsner PG. Gallagher G. Structural characterization of the distal 5Πflanking region of the Interleukin-10 gene. Genes & Immunity 2001,2/4: 181-190

7. Vockerodt M., Tesch H., Kube D. Epstein-Barr Virus latent membrane protein-1 activates CD25 expression in lymphoma cells involving the NFkB pathway. Genes & Immunity 2001 2: 433-441

8. Draube A., Pfister R., Vockerodt M., Schuster S., Kube D., Diehl V., Tesch H. Immunomagnetic enrichment of CD138+ cells from weakly infiltrated myeloma patient samples enables the determination of the tumor clone-specific IgH rearrangement Ann Hematol, 2001; 80: 83-89

9. J. Eskdale, J. Peat, D. Kube, R.C. Stuart, G. Gallagher. "The human interleukin-10 (IL-10) locus : Identification of four IL-10 family members in a cluster within 140kb on chromosome 1q31." Gastroenterology, 2001;120 (5): S1621

10. J. Eskdale, D. Kube, J. Peat, G. Gallagher. "The human interleukin-10 (IL-10) locus: Mapping of novel structural homologues of IL-10 reveals a cluster of four IL-10 family members within approximately 140kb on chromosome 1Q31-32." Arth. Rheum, 2000; 43: (9) S391-S391

11. J. Eskdale, D. Kube, J. Peat, G. Gallagher. "The human interleukin-10 (IL-10) locus: Mapping of novel structural homologues of IL-10 reveals a cluster of four IL-10 family members within approximately 140kb on chromosome 1Q31-32." Arth. Rheum, 2000; .43: (9) S391-S391

12. Hess S; Smola H; Sandaradura De Silva U; Hadaschik D; Kube D; Baldus SE; Flucke U; Pfister H. Loss of IL-6 receptor expression in cervical carcinoma cells inhibits autocrine IL-6 stimulation: abrogation of constitutive MCP-1 production. J Immunol. 2000,165(4): 1939-48

13. Kube D., Laser H., von Knethen A., Tesch H. The AT-rich region between -56 to -68 is important for the promoter activity of Interleukin-10 in Epstein-Barr Virus positive Burkitt's lymphoma cells. Genes & Immunity. 1999, 1, 105-114

14. Kube D., Vockerodt M., Haier B., Weber O., Hell K., Wolf J, Müller-Lantzsch N., Grässer F., Kieff E., Diehl V., Tesch H., EBNA1 activates the IL2-receptor a-chain in the Hodgkins derived cell line L428. J Virology 1999, 73/2; 1630-1636

15. Horn PA, Tesch H, Staib P, Kube D, Diehl V, Voliotis D. Expression of Ac133, a novel hematopoietic precursor antigen on acute myeloid leukemias. Blood, 1999 93, 1435-1436.

16. Vockerodt M., Soares M., Kanzler H., Küppers R., Kube D., Hansmann ML, Diehl V., Tesch H. Dissemination and persistence of clonal Hodgkin and Reed-Sternberg cells in relapsed Hodgkins disease. Blood, 1998 92/8, 2899-2907.

17. von Knethen A., Abts H., Kube D., Tesch H. p56lck is expressed in Burkitts lymphoma cell lines. Leukemia and Lymphoma, 1997, 26, 551-562

18. Eskdale J., Kube D., Tesch H., Gallagher G. Mapping the human IL10 gene and further characterization of the 5' flanking sequence. Immunogenetics 1997, 46, 120-128.

19. Bohlen H., Manzke O., Titzer S., Lorenzen J., Kube D., Engert A., Abken H., Wolf J., Diehl V., Tesch H. Prevention of Epstein-Barr virus induced human B-cell lymphomas in severe combined immunodeficent mice treated with CD3xCD19 bispecific antibodies, CD28 monospecific antibodies and autologous T-cells. Cancer Research, 1997, 57/9, 1704-9

20. Eskdale J., Kube D., Gallagher G. A second polymorphic dinucleotide repeat in the 5'-flanking region of the human IL10 gene. Immunogenetics 1996, 45/1, 82-3.

21. Klein S., Kube D., Abts H., Tesch H. Promotion of IL-8, IL-10, TNF-a and TNF-ß production by EBV infection. Leukemia Research 1996, 20/8, 633-6

22. Westermann F., Kube D., Engert A., Staib P., Diehl V., Bohlen H., Tesch H. Interleukin 10 inhibits cytokine production of human acute myeloid leukemias. Ann Oncol, 1996, 7/4, 397-404

23. Kube D, Platzer C, von Knethen A, Hafner M, Tesch H, Diehl V, The activity of the human interleukin 10 promoter in Epstein-Barr-Virus positive Burkitt Lymphoma cells. Cytokine 1995 , 7 , 1-7

Updated March 2003