Dirk Homann

M.D., M.A., Assistant Professor,  Frei Universität Berlin 

Current Research

My lab is interested in immunological memory, autoimmunity and persistent viral disease. The common theme among these topics is a focus on T cell immunity under conditions where specific T cells provide protection upon reencounter with a pathogen (T cell memory), may cause pathology (autoimmunity), or are impaired in their capacity to control an infection (persistent viral disease). These areas are further united by an experimental approach that aims to assure the pertinence of research endeavors by balancing an appropriate systemic complexity with the feasibility to analyze and manipulate T cell immunity in detail. The experimental system used in the majority of our studies employ "natural" host-pathogen interactions with an experimental emphasis on identification, characterization, localization, isolation and manipulation of specific T cells.

1. T cell memory: Among the most striking attributes of adaptive immunity is the phenomenon of immunological memory, the basis for enhanced protection against disease upon re-exposure to previously encountered pathogens and the efficacy of vaccination as a tool for global control of infectious diseases. Although specific antibody titers often correlate well with protective immunity, control of most viral and many bacterial infections requires the participation of T cells.

T cell memory is an active process that regulates the preservation of specific memory T cell populations in a dynamic environment. As such, specific memory T cells are subject to a dynamic balance between A. cellular longevity and programmed death (apoptosis), B. gradual maturation and age-associated impairments (senescence), C. rest and proliferative self-renewal (homeostatic proliferation) as well as D. tissue residence and migration. Our work aims to understand the phenomenology and mechanistic foundation of this balance by studying the generation, regulation and preservation of T cell immunity in response to selected viruses (lymphocytic choriomeningitis virus [LCMV], vesicular stomatitis virus [VSV] and others) and bacteria. Current projects include the identification and characterization of cytokines involved in the differential regulation of specific CD4+ and CD8+ T cell memory as well as a study of the extended maturation process of established T cell memory.

2. Persistent Viral Disease: Chronic viral infections continue to present major public health problems and pose a particular challenge to the immune system. Failure to effectively control infections with viruses such as HIV, CMV, EBV or hepatitis B and C results in the persistence of virus, viral proteins or genes that may coexist indefinitely in the presence of an immune response that can be impaired to varying degrees. The precise balance between persisting virus and immune response depends on multiple factors such as nature of the infecting virus, route of infection and initial viral burden as well as the immune status of the infected host. The interplay between these parameters ultimately determines the spectrum of possible clinical symptoms associated with viral disease. Using the LCMV system, we are developing projects to further investigate the impact of permanent or protracted viral persistence on the generation and maintenance of heterologous and homologous T cell immunity. We are also planning to study the role of viral persistence in promotion or prevention of autoimmune diabetes.

Recent Publications

Click Here For An Updated List Of Dr. Homann's Publications

Selected publications (T cell memory)

Lenz, D.C., S.K. Kurz, E. Lemmens, S.P. Schoenberger, J. Sprent, M.B.A. Oldstone, D. Homann. Interleukin-7 regulates basal homeostatic proliferation of antiviral CD4+ T cell memory. submitted (2004) 

De Boer, R.J., D. Homann, A.S. Perelson. Different dynamics of CD4+ and CD8+ T cell responses during and after acute LCMV infection. J. Immunol. 171:3928-3935 (2003) 

Homann, D., M.B.A. Oldstone. Maintaining immunity: a tale of two T cell populations. Directions in Science 1:21-24 (2002) 

Homann, D., L. Teyton, M.B.A. Oldstone. Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory. Nat. Med. 7:913-919 (2001)

Selected publications (persistent viral disease) 

Homann, D., D. McGavern, M.B.A. Oldstone. Visualizing the viral burden: phenotypic and functional alterations of T cells and antigen-presenting cells during persistent infection. J. Immunol. in press (2004) 

Homann, D. Immunocytotherapy. In: Arenaviruses II, Curr. Top. Microbiol. Immunol. 263:43-65, M.B.A. Oldstone, ed. (2002) 

Homann, D., D.P. Berger, M.B.A. Oldstone. Defining parameters for successful immunocytotherapy of persistent viral infection. Virology 266:257-263 (2000) 

Homann, D., A. Tishon, D.P. Berger, W.O. Weigle, M.G. von Herrath, M.B.A. Oldstone. Evidence for an underlying CD4 helper and CD8 T cell defect in B cell-deficient mice: failure to clear persistent virus infection after adoptive immunotherapy with virus-specific memory cells from μMT/μMT mice. J. Virol. 72:9208-9216 (1998)