Heath laboratory: CD8 T lymphocytes, dendritic cells, self tolerance and immunity

Research Overview

Staff

Dr Gayle Davey, SRO
Dr Daniel Fernandez Ruiz, RO
Nazanin Ghazanfari, RO
Lauren Holz, RO
Melanie Damtsis, Research Assistant
Ming Li, Research Assistant
Jyh Liang Hor, PhD Student
Alex Kato, PhD Student
Marie Greyer, PhD student
Wei Yi Ng, PhD student

Funding

The Heath Lab is broadly interested in the initiation of immunity and the role and function of CD8+ killer T cells. CD8 killer T cells are critical for protection against viral and parasitic infections and tumour development, but when inappropriately activated can attack the body's own tissues leading to autoimmune disease. The lab uses novel models and cellular immunology tools to understand and dissect CD8 killer T cell activation and function. An exciting new aspect to the research repertoire is the ability to directly visualise cellular interactions with 2-photon microscopy. Current research is examining cytotoxic T cell function in a number of different studies as described below in major research projects.

  1. Improved vaccines by targeting to dendritic cells
  2. Malaria and Tissue resident memory T cells (TRM) in the Liver
  3. Vaccination against Liver-stage Plasmodium for Malaria Prevention
  4. Self-tolerance: interactions between thymic stroma and dendritic cells

Projects in conjunction with the Mueller group

  1. Intravital imaging of malaria-specific T cell responses in the brain during experimental cerebral malaria infection
  2. Imaging the priming of CD8 killer T cell responses to Herpes Simplex Virus-1 skin infection
  3. Imaging effector and memory T cell responses in the skin following Herpes Simplex Virus-1 infection

Projects in conjunction with the Bedoui group

  1. Dendritic cell maturation following different microbial stimulation

Research Publications

  1. Hor JL, Whitney PG, Zaid A, Brooks AG, Heath WR, Mueller SN. Spatiotemporally distinct interactions with dendritic cell subsets facility-ates CD4+ and CD8+ T cell activation to localized viral infection. Immunity In press.
  2. Kato Y, Zaid A, Davey GM, Mueller SN, Nutt SL, Zotos D, Tarlinton DM, Shortman K, Lahoud MH, Heath WR, Caminschi I. Targeting Antigen to Clec9A Primes Follicular Th Cell Memory Responses Capable of Robust Recall. Journal of Immunology 2015; 195: 1006-14.
  3. Li J, Ahmet F, Sullivan LC, Brooks AG, Kent SJ, De Rose R, Salazar AM, Reis E Sousa C, Shortman K, Lahoud MH, Heath WR, Caminschi I. Antibodies targeting Clec9A promote strong humoral immunity without adjuvant in mice and non-human primates. Eur J Immunol 2015; 45: 854-64.
  4. Lau LS, Fernandez-Ruiz D, Mollard V, Sturm A, Neller MA, Cozijnsen A, Gregory JL, Davey GM, Jones CM, Lin YH, Haque A, Engwerda CR, Nie CQ, Hansen DS, Murphy KM, Papenfuss AT, Miles JJ, Burrows SR, de Koning-Ward T, McFadden GI, Carbone FR, Crabb BS, Heath WR. CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria. PLoS Pathogens 2014; 10: e1004135.
  5. Zaid A, Mackay LK, Rahimpour A, Braun A, Veldhoen M, Carbone FR, Manton JH, Heath WR, Mueller SN. Persistence of skin-resident memory T cells within an epidermal niche. Proc Natl Acad Sci USA 2014; 111: 5307-12.
  6. Davey GM, Mueller SN, van Vliet C, Gigowski M, Zaid A, Davies B, Carbone FR, Heath WR. Identification of a MHC I-restricted epitope of DsRed in C57BL/6 mice. Mol Immunol 2013; 53: 450-2.
  7. Lahoud MH, Ahmet F, Zhang JG, Meuter S, Policheni AN, Kitsoulis S, Lee CN, O'Keeffe M, Sullivan LC, Brooks AG, Berry R, Rossjohn J, Mintern JD, Vega-Ramos J, Villadangos JA, Nicola NA, Nussenzweig MC, Stacey KJ, Shortman K, Heath WR, Caminschi I. DEC-205 is a cell surface receptor for CpG oligonucleotides. Proc Natl Acad Sci USA 2012; 109: 16270-5.
  8. Lau LS, Fernandez Ruiz D, Davey GM, de Koning-Ward TF, Papenfuss AT, Carbone FR, Brooks AG, Crabb BS, Heath WR. Blood-stage Plasmodium berghei infection generates a potent, specific CD8+ T-cell response despite residence largely in cells lacking MHC I processing machinery. J Infect Dis 2011; 204: 1989-96.
  9. 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.
  10. Hubert FX, Kinkel SA, Davey GM, Phipson B, Mueller SN, Liston A, Proietto AI, Cannon PZ, Forehan S, Smyth GK, Wu L, Goodnow CC, Carbone FR, Scott HS, Heath WR. Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance. Blood 2011; 118: 2462-72.
  11. Lundie RJ, Young LJ, Davey GM, Villadangos JA, Carbone FR, Heath WR, Crabb BS. Blood-stage Plasmodium berghei infection leads to short-lived parasite-associated antigen presentation by dendritic cells. Eur J Immunol 2010; 40: 1674-81.
  12. Cutting edge: priming of CD8 T cell immunity to herpes simplex virus type 1 requires cognate TLR3 expression in vivo. Davey GM, Wojtasiak M, Proietto AI, Carbone FR, Heath WR, Bedoui S. Journal of Immunology 2010; 184: 2243-6.
  13. Reviews or commentaries

  14. Bedoui S, Heath WR. Kr├╝ppel-ling of IRF4-Dependent DCs into Two Functionally Distinct DC Subsets. Immunity 2015; 42: 785-7.
  15. Heath WR, Carbone FR. The skin-resident and migratory immune system in steady state and memory: innate lymphocytes, dendritic cells and T cells. Nat Immunol 2014; 14: 978-85.
  16. Caminschi I, Meuter S, Heath WR. DEC-205 is a cell surface receptor for CpG oligonucleotides. Oncoimmunology 2013; 2: e23128.
  17. Mueller SN, Gebhardt T, Carbone FR, Heath WR. Memory T cell subsets, migration patterns, and tissue residence. Ann Rev Immunol 2013; 31: 137-61.
  18. Heath WR, Mueller SN. Hair follicles: gatekeepers to the epidermis. Nat Immuno 2012; 13: 715-7.
  19. Caminschi I, Maraskovsky E, Heath WR. Targeting Dendritic Cells in vivo for Cancer Therapy. Front Immunol 2012; 3: 13.
  20. Bedoui S, Heath WR. A local role for CD103+ dendritic cells in atherosclerosis. Immunity 2011; 35: 665-7.
  21. Carbone FR, Heath WR. Cross-priming: its beginnings. J Immunol 2010; 185 : 1353-4.
  22. Shortman K, Heath WR. The CD8+ dendritic cell subset. Immunol Rev 2010; 234: 18-31.