Faculty of Medicine, Dentistry and Health Sciences Department of Microbiology and Immunology

Carbone Laboratory

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Include: Research Interests | Major Research Projects | Laboratory Staff | Recent Publications

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Professor Frank Carbone's Home Page

Research Interests

Our research focuses on the immune response after herpes simplex virus (HSV) infection. HSV is extremely widespread in the human population. Primary infection commonly involves the mouth and/or throat in HSV type 1 (HSV-1) infections and the genitalia in HSV type 2 (HSV-2) infections. Immunity to HSV involves many highly complex interactions between various cells of the immune system and virus-infected cells in the skin, mucosa and the nerves.

We have found that the cytotoxic T lymphocytes (CTLs) are important in the recovery from primary, or lytic, infection with HSV and potentially important in maintaining virus in a quiescent or latent form. We have shown that these T cells, which circulate through the blood and lymph, are activated very quickly in the local lymph nodes draining infected tissues. This CTL “priming” is totally dependent on dendritic cells and, in particular, a blood-derived subset marked by the expression surface expressed CD8. The identification of this particular population was surprising, given the long-held view that skin Langerhans cells would be the key drivers in this type of immunity.

We have begun to investigate how the interplay between T cells and dendritic cells generate effective and long-lived immunity, especially in cases of infections of the skin.

Our expertise is in dendritic cell and T cell biology, herpes simplex virus infection and the immunobiology of the skin during disease and immunity. The laboratory is funded through an NHMRC Program grant “Antigen presentation, recognition and the immune response” held with Dr. William Heath and Prof. Ken Shortman (both from the Walter and Eliza Hall Institute), Prof. Jamie Rossjohn (Monash University) and Prof. Jim McCluskey and Dr. Andrew Brooks (both from the Department of Microbiology and Immunology at the University of Melbourne).

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Major Research Projects

  1. Examination of CD8+ T cell memory to cutaneous HSV infection
  2. Involvement of dendritic cells on cytotoxic T lymphocyte priming
  3. HSV Latency
  4. Cross-presentation

Laboratory Staff

Laboratory Head

Professor Francis (Frank) Carbone
email: fcarbone@unimelb.edu.au

Claerwen Jones PhD (Program Manager)
Thomas Gebhardt MD PhD (Visiting Research Fellow)
Liv Eidsmo MD PhD (Visiting Research Fellow)
Dr Ali Zaid (RO)
Dr Laura Mackay (RO)
Serrin Rowarth (Laboratory Technican)

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Recent Publications

List of Publications prior to 2007

  1. Bedoui S, Whitney P, Waithman J, Eidsmo L, Wakim L, Caminschi I, Allan R, Wojtasiak M, Shortman K, Carbone F, Brooks A, Heath W. Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nature Immunology 2009; 10: 488-495.
  2. Eidsmo L, Allan R, Caminschi I, van Rooijen N, Heath W, Carbone F. Differential migration of epidermal and dermal dendritic cells during skin infection. Journal of Immunology 2009; 182: 3165-3172
  3. Gebhardt T, Wakim L, Eidsmo L, Reading P, Heath W, Carbone F. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nature Immunology 2009; 10: 524-530.
  4. Parish IA, Waithman J, Davey GM, Belz GT, Mintern J, Kurts C, Sutherland RM, Carbone F, Heath W. Tissue destruction caused by cytotoxic T lymphocytes induces deletional tolerance. Proc Nat Acad Sc (USA) 2009; 106: 3901-3906.
  5. Lundie R, de Koning-Ward T, Davey G, Nie C, Hansen D, Lau L, Mintern J, Belz G, Scholfield L, Carbone F, Villadangos J, Crabb B, Heath W. Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8alpha+ dendritic cells. Proc Nat Acad Sc (USA) 2008;105: 14509-14514.
  6. Wakim L, Jones C, Gebhardt T, Preston C, Carbone F. CD8+ T-cell attenuation of cutaneous herpes simplex virus infection reduces the average viral copy number of the ensuing latent infection. Immunology and Cell Biology 2008; 86: 666-675.
  7. Wakim L, Gebhardt T, Heath W, Carbone F. Cutting edge: Local recall responses by memory T cells newly recruited to peripheral nonlymphoid tissues. Journal of Immunology 2008; 181: 5837-5841.
  8. Waithman J, Gebhardt T, Davey G, Heath W, Carbone F. Cutting edge: Enhanced IL-2 signaling can convert self-specific T cell response from tolerance to autoimmunity. Journal of Immunology 2008; 180: 5789-5793.
  9. Wakim LM, Waithman J, van Rooijen N, Heath WR, Carbone FR. Dendritic cell-induced memory T cell activation in nonlymphoid tissues. Science 2008; 319: 198-202.
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  10. Fernandez M, Evans I, Hassan E, Carbone F, Jones C. Neonatal CD8+ T cells are slow to develop into lytic effectors after HSV infection in vivo. European Journal of Immunology 2008; 38: 102-113.
  11. Barr DP, Belz G, Reading P, Wojtasiak M, Whitney PG, Heath W, Carbone F, Brooks A. A role for plasmacytoid dendritic cells in the rapid IL-18-dependent activation of NK cells following HSV-1 infection. European Journal of Immunology 2007; 37: 1334-42.
  12. Mintern J, Guillonneau C, Carbone F, Doherty P, Turner S. Cutting edge: Tissue-resident memory CTL down-regulate cytolytic molecule expression following virus clearance. Journal of Immunology 2007; 179: 7220-7224.
  13. Belz G, Bedoui S, Kupresanin F, Carbone F, Heath W. Minimal activation of memory CD8+ T cell by tissue-derived dendritic cells favors the stimulation of naive CD8+ T cells. Nature Immunology 2007; 8: 1060-1066.
  14. Stock AT, Mueller S, Sadler L, Heath W, Carbone F, Jones C. Optimization of TCR transgenic T cells for in vivo tracking of immune responses. Immunology and Cell Biology 2007; 85: 394-396.
  15. Villadangos JA, Heath WR, Carbone F. Outside looking in: the inner workings of the crosspresentation pathway within dendritic cells. Trends in Immunology (formerly Immunology Today) 2007; 28: 45-47.
  16. Waithman JC, Allan R, Kosaka H, Azukizawa H, Shortman K, Lutz M, Heath W, Carbone F, Belz G. Skin-derived dendritic cells can mediate deletional tolerance of Class I-restricted self-reactive T cells. Journal of Immunology 2007; 179: 4535-4541.

 

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