A12

A12: Summary

Chronic viral infections like HIV, CMV or chronic hepatitis are characterized by antigen persistence, leading to immune cell exhaustion, immunosenescence, and chronic immune activation. We hypothesise that extracellular adenine nucleotides/nucleosides play important roles in regulating these processes. In this project, we will monitor the expression patterns, regulation and interaction of CD39, CD73, P2X7, and ADO receptors on lymphocyte subsets in peripheral blood and tissue samples from healthy donors and patients with different stages of chronic viral infection. We will use fluorescent sensors to visualize local ATP concentrations at the cell surface and in other compartments of immune cells.

Prof. Dr. Friedrich Haag

Selected publications

 

  1. Kaschubowski KE, Kraft AE, Nikolaev VO, Haag F (2020) Using FRET-Based Fluorescent Sensors to Monitor Cytosolic and Membrane-Proximal Extracellular ATP Levels. Methods Mol Biol 2041:223-231
  2. Johnsen B, Kaschubowski KE, Nader S, Schneider E, Nicola JA, Fliegert R, Wolf IMA, Guse AH, Nikolaev VO, Koch-Nolte F, Haag F (2019) P2X7-mediated ATP secretion is accompanied by depletion of cytosolic ATP. Purinergic Signal 15:155-166
  3. Fumey W, Koenigsdorf J, Kunick V, Menzel S, Schütze K, Unger M, Schriewer L, Haag F, Adam G, Oberle A, Binder M, Fliegert R, Guse A, Zhao YJ, Lee HC, Malavasi F, Goldbaum F, van Hegelsom R, Stortelers C, Bannas P, Koch-Nolte F (2017) Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo. Sci Reports 7:14289
  4. Kim ES, Ackermann C, Toth I, Dierks P, Eberhard JM, Wroblewski R, Scherg F, Geyer M, Schmidt RE, Beisel C, Bockhorn M, Haag F, van Lunzen J, Schulze Zur Wiesch J (2017) Down-regulation of CD73 on B cells of patients with viremic HIV correlates with B cell activation and disease progression. J Leukoc Biol. 101: 1263-1271.
  5. Panda R, Krieger T, Hopf L, Renne T, Haag F, Rober N, Conrad K, Csernok E, Fuchs TA (2017) Neutrophil Extracellular Traps Contain Selected Antigens of Anti-Neutrophil Cytoplasmic Antibodies. Front Immunol 8:439.
  6. Schieferdecker A, Oberle A, Thiele B, Hofmann F, Gothel M, Miethe S, Hust M, Braig F, Voigt M, von Pein UM, Koch-Nolte F, Haag F, Alawi M, Indenbirken D, Grundhoff A, Bokemeyer C, Bacher U, Kroger N, Binder M (2016) A transplant immunome deep sequencing and screening platform defines a unique targetable epitope fingerprint of multiple myeloma. Blood 127: 3202-3214.
  7. Teege S, Hann A, Miksiewicz M, MacMillan C, Rissiek B, Buck F, Menzel S, Nissen M, Bannas P, Haag F, Boyer O, Seman M, Adriouch S, Koch-Nolte F (2015) Tuning IL-2 signaling by ADP-ribosylation of CD25. Sci Rep 5:8959.
  8. Schmidt T, Paust HJ, Krebs CF, Turner JE, Kaffke A, Bennstein SB, Koyro T, Peters A, Velden J, Hunemorder S, Haag F, Steinmetz OM, Mittrücker HW, Stahl RA, Panzer U (2015) Function of the Th17/interleukin-17A immune response in murine lupus nephritis. Arthritis Rheumatol 67:475-487.
  9. Rissiek A, Baumann I, Cuapio A, Mautner A, Kolster M, Arck PC, Dodge-Khatami A, Mittrucker HW, Koch-Nolte F, Haag F, Tolosa E (2015) The expression of CD39 on regulatory T cells is genetically driven and further upregulated at sites of inflammation. J Autoimmun 58:12-20.
  10. Menzel S, Rissiek B, Bannas P, Jakoby T, Miksiewicz M, Schwarz N, Nissen M, Haag F, Tholey A, Koch-Nolte F (2015) Nucleotide-Induced Membrane-Proximal Proteolysis Controls the Substrate Specificity of T Cell Ecto-ADP-Ribosyltransferase ARTC2.2. J Immunol 195:2057-2066.

PD Dr. Julian Schulze zur Wiesch

Selected publications

 

  1. Eberhard JM, Angin M, Passaes C, Salgado M, Monceaux V, Knops E, Kobbe G, Jensen B, Christopeit M, Kröger N, Vandekerckhove L, Badiola J, Bandera A, Raj K, van Lunzen J, Hütter G, Kuball JHE, Martinez-Laperche C, Balsalobre P, Kwon M, Díez-Martín JL, Nijhuis M, Wensing A, Martinez-Picado J, Schulze Zur Wiesch J, Sáez-Cirión A (2020) Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1. Sci Transl Med 12:eaay9355
  2. Wittner M, Schlicker V, Libera J, Bockmann JH, Horvatits T, Seiz O, Kummer S, Manthey CF, Hüfner A, Kantowski M, Rösch T, Degen O, Huber S, Eberhard JM, Schulze Zur Wiesch J (2019) Comparison of the integrin α4β7 expression pattern of memory T cell subsets in HIV infection and ulcerative colitis. PLoS One14:e0220008
  3. Kim ES, Ackermann C, Tóth I, Dierks P, Eberhard JM, Wroblewski R, Scherg F, Geyer M, Schmidt RE, Beisel C, Bockhorn M, Haag F, van Lunzen J, Schulze Zur Wiesch J (2017) Down-regulation of CD73 on B cells of patients with viremic HIV correlates with B cell activation and disease progression. J Leukoc Biol 101:1263-1271.
  4. Dierks P, Wroblewski R, Eberhard JM, Martrus G, Degen O, Hertling S, Schmiedel S, Lunemann S, Hüfner A, Lohse AW, Altfeld M, van Lunzen J, Schulze Zur Wiesch J (2017) Brief Report: Increased Frequency of CD39+ CD56bright Natural Killer Cells in HIV-1 Infection Correlates With Immune Activation and Disease Progression. J Acquir Immune Defic Syndr 74:467-472.
  5. Mackroth MS, Abel A, Steeg C, Schulze Zur Wiesch J, Jacobs T (2016) Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function. PLoS Pathog 12:e1005909.
  6. Eberhard JM, Kummer S, Hartjen P, Hüfner A, Diedrich T, Degen O, Lohse AW, van Lunzen J, Schulze Zur Wiesch J (2016) Reduced CD161+ MAIT cell frequencies in HCV and HIV/HCV co-infection: Is the liver the heart of the matter? J Hepatol 65:1261-1263.
  7. Tóth I., Le A., Hartjen P, Thomssen A, Matzat V, Lehmann C., Scheurich C., Beisel C, Busch P , Degen O, Lohse A, Eiermann T, Fätkenheuer G, Meyer-Olson G, Bockhorn M, Hauber J, van Lunzen J, Schulze zur Wiesch J (2013) Down-regulation of the 5’-Ectonucleotidase CD73 of CD8+ T cells of HIV infected patients correlates with immune activation and T cell exhaustion. J Leukoc Biol 94:551-561.
  8. Lindqvist M, van Lunzen J, Soghoian DZ, Kuhl BD, Ranasinghe S, Kranias G, Flanders MD, Cutler S, Yudanin N, Muller MI, Davis I, Farber D, Hartjen P, Haag F, Alter G, Schulze zur Wiesch J, Streeck H (2012) Expansion of HIV-specific T follicular helper cells in chronic HIV infection. J Clin Invest 122:3271-3280.
  9. Schulze zur Wiesch J*, Ciuffreda D *, Lewis-Ximenez L, Kasprowicz V, Nolan B, Streeck H, Aneja J, Reyor L, Allen T, Lohse A, McGovern B, Chung R, Kwok W, Kim A, Lauer G (2012) Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence. J Exp Med 209:6175.
  10. Schulze zur Wiesch J *, Thomssen A*, Hartjen P, Tóth I, Lehmann C, Meyer-Olson D, Colberg K, Frerk S, Babikir D, Schmiedel S, Degen O, Mauss S, Rockstroh J, Staszewski S, Khaykin P, Strasak A, Lohse AW, Fätkenheuer G, Hauber J, van Lunzen J (2011) Comprehensive Analysis of Frequency and Phenotype of T Regulatory Cells in HIV Infection: CD39 Expression of FoxP3+ T Regulatory Cells Correlates with Progressive Disease. J Virol 85:1287-1297.

Our Team

Prof. Dr. Friedrich Haag

Insitute of Immunology

University Medical Centre Hamburg-Eppendorf (UKE)

PD Dr. Julian Schulze zur Wiesch

1. Department of Medicine

University Medical Center Hamburg-Eppendorf (UKE)

M.Sc. Klaus Kaschubowski

Insitute of Immunology

University Medical Centre Hamburg-Eppendorf (UKE)

M.Sc. Parimah Ahmadi

1. Department of Medicine

University Medical Center Hamburg-Eppendorf (UKE)

M.Sc. Samantha Wittke

Insitute of Immunology

University Medical Centre Hamburg-Eppendorf (UKE)

M.Sc. Sana Javed

Insitute of Immunology

University Medical Centre Hamburg-Eppendorf (UKE)

Antonia Lehmann

Insitute of Immunology

University Medical Centre Hamburg-Eppendorf (UKE)

Contact

University Medical Center Hamburg-Eppendorf 
Department of Biochemistry and Molecular Cell Biology 
Martinistrasse 52
20246 Hamburg

Scientific Coordinator

Dr. Björn-Philipp Diercks
Fon: +49  (0) 40 7410 54338
E-Mail: b.diercks©uke.de

Administration

Laura Mitsching
Fon: +49  (0) 40 7410 50301
E-Mail: l.mitsching©uke.de