Thomas Gebhardt MD, PhD
|Academic Degrees||Contact Details|
|2002: Graduation from Medicine (MBBS equivalent)
2004: MD, Hanover Medical School, Germany
2005: PhD, Hanover Biomedical Research School, Germany
|Tel: +61 3 8344 6132
Fax: +61 3 8347 1540
Room 5.19B, Department of Microbiology and Immunology
2012 – present: Senior Research Fellow (Level C), Department of Microbiology and Immunology, The University of Melbourne, Australia
2010 – present: NHMRC Career Development Fellow (Level 1), Department of Microbiology and Immunology, The University of Melbourne, Australia
2007 – 2009: Senior Research Officer (Level B), Department of Microbiology and Immunology, The University of Melbourne, Australia
2005 – 2007: Postdoctoral Fellow (German Research Foundation), Department of Microbiology and Immunology, The University of Melbourne, Australia
2004 – 2005: Assistant Doctor, Department of Gastroenterology, Hepatology and Endocrinology, Hanover Medial School, Germany
2003 – 2004: Internship, Department of Gastroenterology, Hepatology and Endocrinology, Hanover Medial School, Germany
Thomas obtained his MD and his PhD from the Hanover Medical School and the Hanover Biomedical Research School in Germany, respectively. Both theses were based on research work in the area of mucosal immunology with a particular focus on the biology of human intestinal mast cells. Thomas joined the Department of Microbiology and Immunology in 2005 as a Fellow of the German Research Foundation and was awarded a NHMRC Career Development Award in 2009. His current research is concerned with the role of T cells, dendritic cells and mast cells in the control of peripheral virus infections and autoimmunity.
T cells in peripheral immunity
T cells are key immune cells involved in protection from a broad range of microbes. T cells exist as distinct subsets that have specialised functions and roles during immune responses. We wish to understand how these diverse functions of T cells are regulated within peripheral tissues during the early stages of microbial infection. Furthermore, we are interested in the generation and regulation of so-called memory T cells that emerge following the numerical contraction of the pathogen-specific T cell pool once infection has resolved. Memory T cells are key to protection from re-infection and continuously patrol diverse organs for invading pathogens. We are interested in this patrolling or immuno-surveillance function of memory T cells and are trying to understand how different factors can “imprint” organ-tropic migration in T cells. Separately, we and others have recently demonstrated that certain peripheral tissues can support the generation of a distinct subset of killer memory T cells now widely referred to as tissue-resident memory T cells (TRM). TRM cells functionally differ from their circulating counterparts found in the blood and permanently reside in tissues such as skin and mucosa. Given that these barrier tissues are common portals of entry for pathogens, TRM cells are strategically well positioned to rapidly control re-infection. We are interested in understanding the generation and persistence of TRM cells in peripheral tissues and in harnessing the protective potential of these cells with novel immunisation strategies. Our research program is funded by the NHMRC project grants APP628423 “Effective T cell memory in peripheral organs” (Thomas Gebhardt) and APP1003717 “The role of helper T cells in immunity to HSV-1” (Andrew Brooks and Thomas Gebhardt) as well as infrastructure and research support grants from the University of Melbourne.
Figure 1: Virus-specific memory T cells (shown in green) persist in the epidermal
layer of the skin (indicated by red keratin staining). Skin was analysed two weeks
after skin infection with herpes simplex virus-1 (HSV-1).
Figure 2: Virus-specific memory T cells persist in previously infected skin and
display a unique phenotype. Analysis of memory T cells in spleen and previously
infected (ipsilateral) or control (contralateral) skin (>1 year after HSV-1
infection). Rectangles indicate virus-specific memory cells as CD8+CD45.1+ or
Va2+CD45.1+ events (upper panel). Lower panel shows the expression of CD103
and CD69 by circulating (spleen) and tissue-resident (skin) memory T cells.
Dr Laura Mackay (Research Officer, with Carbone lab)
Dr Asolina Braun (Research Officer, with Carbone lab)
Dr Sanda Stankovic (Research Officer, with Brooks lab)
Nathan McBain (Research Assistant)
Bethany McLeod (PhD student)
Nicholas Collins (PhD student)
Chris Harpur (PhD student, with Brooks lab)
Ming-Li Hafon (Honours student, successful completion)
- Gebhardt T, Mackay LM.
Local immunity by tissue-resident CD8+ memory T cells.
Front Immunol 2012; 3: 340
This review article provides a comprehensive discussion of the biology of tissue-resident CD8+ memory T cells and their role in infection control.
- Mackay LK, Stock AT, Ma JZ, Jones CM, Kent SJ, Mueller SN, Heath WR, Carbone FR, Gebhardt T.
Long-lived epithelial immunity by tissue-resident memory T (TRM) cells in the absence of persisting local antigen presentation.
Proc Natl Acad Sci USA 2012; 109: 7037-42.
This paper describes an approach for the generation of high numbers of tissue-resident CD8+ memory T cells using a combination of T cell activation and localised antigen non-specific inflammation. We show that epithelial memory T cells generated in this fashion protect from de novo virus infection in skin and mucosa.
- Gebhardt T, Whitney PG, Zaid A, Mackay LK, Brooks AG, Heath WR, Carbone FR, Mueller SN.
Different patterns of peripheral migration by memory CD4(+) and CD8(+) T cells.
Nature 2011; 477: 216-9.
This paper describes major differences in peripheral migration of virus-specific CD4+ and CD8+ memory T cells. It reinforces the concept that permanently tissue-resident CD8+ memory T cells exist as a distinct memory cell subset in disequilibrium with their circulating counterparts.
- Bedoui S, Gebhardt T.
Interaction between dendritic cells and T cells during peripheral virus infections: a role for antigen presentation beyond lymphoid organs?
Curr Opin Immunol 2011; 23: 124-30.
This review article discusses the functional consequences of dendritic cell-T cell interactions in both lymphoid and non-lymphoid tissues during virus infection.
- Gebhardt T, Wakim LM, Eidsmo L, Reading PC, Heath WR, Carbone FR.
Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus.
Nat Immunol 2009; 10: 524-30.
This paper identifies and coins tissue-resident memory T cells as important contributors to immediate local immunity against re-infection. It provides evidence that virus-specific memory CD8+ T cells form a pool of permanently tissue-resident memory cells at sites of previous infection.
- Waithman J*, Gebhardt T*, Davey GM, Heath WR, Carbone FR. (*Equal contribution)
Cutting edge: Enhanced IL-2 signaling can convert self-specific T cell response from tolerance to autoimmunity.
J Immunol 2008; 180: 5789-93.
This paper describes differences in the auto-aggressive potential between naïve and memory CD8 T cells in a model system of skin autoimmunity.