Bernhard Nocht Institute for Tropical Medicine

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Research>Groups>Tropical Medicine Section >Department of Pathology and
Körber Laboratory for
AIDS Research

Head
Prof. Dr. Paul Racz (-499)

Scientific staff
Dr. Klara Tenner-Racz (-499)
Jill Knips (-494)
Christine Stempell

Support staff
Ingeborg Albrecht (-413)
Gudrun Großschupff (-497)
Anke Kuhfuß
Birgit Raschdorff (-497)
Christa Schulz

Overview - Projects - Publications

Overview

The main topic of the work of the department is the evaluation of the events that take place in the lymphoid tissue during HIV-infection or infection with the simian immunodeficiency virus (SIV) that is a model disease for HIV infection. The lymphoid tissue (e.g., lymph nodes, spleen, gut associated lymphoid tissue) play a central role in the disease caused by these causative agents. Both viruses replicate and persist in the lymphoid tissue leading to the destruction of these important immune organs. Presently, our group deals with two important aspects of HIV infection: (a) we seek information on the deterioration of the gut mucosal immune system that occurs early during HIV infection and assess the possibility whether immunoarchitectural restoration of this system occurs during antiretroviral therapy; and (b) we analyse the persistence of HIV RNA, structural proteins and glycoproteins in the germinal centres of lymph nodes.
In the simian model for HIV-infection our group focus on the following fields: (i) we assess the immunomorphologic aspects of mucosal vaccine candidates which induce mucosal and systemic immunity against SIV; (ii) We investigate the ability of vaccine candidates to bind to bone marrow-derived dendritic cells. These cells are professional antigen-presenting cells which orchestrate immune responses. Thus, delivery of vaccine antigens to these cells is of central importance. (iii) An important task of our group has been the search for nasal associated lymphoid tissue in rhesus macaques. This member of the mucosal immune system has not been described until now. Because nasal immunization gainsinterest in vaccinology the presence or absence of the nasal associated lymphoid tissue is of great importance.
Our research interest is also focused on cutaneous leishmaniasis, an important disease not only in the tropics but also in Mediterranean countries and also among military persons deployed in Southwest/Central Asia.

Projects

Immunopathologic and molecular pathologic changes of the gut-associated lymphoid tissue in HIV-1-infection
Paul Racz and Klara Tenner-Racz
Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under HAART
Paul Racz and Klara Tenner-Racz
Binding of monoclonal antibody raised against bone marrow-derived dendritic cells and loaded with vaccine antigen to lymph node dendritic cells in rhesus macaques.
Klara Tenner-Racz and Paul Racz
Expression of vaccine candidates delivered via the mucosal route of applied intravenously in lymphoid tissue of rhesus macaques.
Klara Tenner-Racz and Paul Racz
Nasal-associated lymphoid tissue in rhesus macaques.
Jill Knips, Paul Racz, Klara Tenner-Racz
Intralesional Regulatory T Cells in Cutaneous Leishmania major Infection of Young Adult Persons.
Marcellus Fischer, Klara Tenner-Racz, Paul Racz

Funding of the research program:

MUVADEN, European Commission

TIP-VAC, European Commission

MUVAPRED, European Commission

GRAND CHALLENGE, Grand Challenges in Global Health Initiative, Foundation for the National Institutes of Health, USA

KOMPETENZNETZE IN DER MEDIZIN HIV/AIDS, Bundesministerium für Bildung und Forschung

Publications

Tenner-Racz K, Stahl-Hennig C, Überla K, Stoiber H, Ignatius R, Heeney J, Steinman RM, Racz P: Early protection against pathogenic virus infection at a mucosal challenge site after vaccination with attenuated simian immunodeficiency virus. Proc. Natl. Acad. Sci. USA 101:3017-3022 2004

Mehandru S, Poles MA, Tenner-Racz K, Horowitz A, Hurley A, Hogan C, Boden D, Racz P, Markowitz M: Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med. 200:761-70 2004

Schmitz JE, Johnson RP, McClure HM, Manson KH, Wyand MS, Kuroda MJ, Lifton MA, Khunkhun RS, McEvers KJ, Gillis J, Piatak M, Lifson JD, Grosschupff G, Racz P, Klara Tenner-Racz K, Rieber EP, Kuus-Reichel K, Gelman RS, Letvin NL, Montefiori DC, Ruprecht RM, Desrosiers RC, Reimann KA : Effect of CD8+ lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239{delta}3-vaccinated rhesus macaques. J Virol. 79:8131-8141.2005

Popovic M, Tenner-Racz K, Pelser C, Stellbrink HJ, van Lunzen J, Lewis G, Kalyanaraman VS, Gallo RC, Racz P : Persistence of HIV-1 structural proteins and glycoproteins in lymph nodes of patients under HAART. Proc Natl Acad Sci USA 102:14807-14812 2005

Mehandru S, Poles, MA, Tenner-Racz K, Jean-Pierre P, Manuelli V, Lopez P, Shet A, Low A, Mohri H, Boden D, Racz P, Markowitz M: Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection. PLoS Medicine 3(11): e484. doi:10.1371/journal.pmed.0040484 Erratum in: PLoS Med. 2006 Dec;3(12):e546.

Mehandru S, Poles MA, Tenner-Racz K, Manuelli V, Lopez P J.-P., Shet A, Low A, Mohri H, Boden D, Racz P, Markowitz M : Mechanisms of gastrointestinal CD4+ T cell depletion during acute and early HIV-1 infection. J Virol 81:599-612 2007

Janowicz DM, Tenner-Racz K, Racz P, Humphreys TL, Schnizlein-Bick C, Fortney KR, Zwickl B, Katz BP, Campbell JJ, Ho DD, Spinola SM: Experimental infection with Haemophilus ducreyi in persons who are infected with HIV does not cause local or augment systemic viral replication. J Infect Dis 195:1443-1451 2007

Georgsson G, Stahl-Hennig C, Tenner-Racz K, Überla K, Stoiber H, Uguccioni M, Dietrich M, Ignatius R, Steinman RM, Racz P: The central nervous system in mucosal vaccination of rhesus macaques with simian immunodeficiency virus Deltanef. Neuropathol Apl Neurobiol 33:644-657 2007

Cagigi A, Mowafi F, Dang LVP, Tenner-Racz K, Atlas A, Grutzmeier S, Racz P, Chiodi F, Nilsson A: Altered expression of the receptor-ligand pair CXCR5/CXCL13 in B-cells during chronic HIV-1 infection. Blood 112:4401-4410 2008

Stahl-Hennig C, Eisenblätter M, Jasny E, Rzehak T, Tenner-Racz K, Trumpfheller C, Salazar AM, Uberla K, Nieto K, Kleinschmidt J, Schulte R, Gissmann L, Müller M, Sacher A, Racz P, Steinman RM, Uguccioni M, Ignatius R: Synthetic double-stranded RNAs are adjuvants for the induction of T helper 1 and humoral immune responses to human papillomavirus in rhesus macaques. PLoS Pathog. 5(4): e1000373. doi:10.1371/journal.ppat. 1000373

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