Understanding the generation of protective memory T cells
Project type
Honours and/or PhD
| Supervisor(s) | Division | |
| (Primary) | Molecular Immunology | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Infection and Immunity | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Molecular Immunology | .(JavaScript must be enabled to view this email address) |
Details of project
Cytotoxic CD8+ T cells (CTLs) play a significant role in the control and removal of tumours and virally infected cells. Upon activation, naive CTLs need to undergo a program of proliferation and functional differentiation that results in the acquisition and regulated expression of multiple effector genes.
Following virus/tumor clearance, effector CTL numbers contract establishing a pool of long-lived, resting memory CTL. Importantly, unlike naïve CTL, memory CTL exhibit rapid effector gene expression upon activation without the need for further differentiation. This enables more rapid control and clearance of subsequent virus infection/tumor challenge. Furthermore, the array of effector molecules expressed by pathogen-specific T cells is an emerging correlate for effective immunity. The molecular processes that underpin the acquisition of effective effector and memory characteristics of T cells are not yet clearly defined.
The aim of this project is to understand the signals that specify the fate decisions of developing CD8+ T cells in in vivo models of virus infection. This is a particularly interesting question with regard to transcription factors such as Irf8, Id2 and E proteins. These data could potentially provide novel molecular signatures that are characteristic of memory CTL thereby providing novel targets for potential therapeutic interventions, or for use as novel immune signatures for evaluation of vaccine efficacy.
Research interests
Our research is focussed on understanding how a subset of white blood cells, called cytotoxic T cells (CTL or CD8 T cells), recognise and remove virally-infected cells from the body following infection. The aim is to identify specific factors that determine how virus-specific killer T cells develop during an infection and how they impact on the establishment of immune memory after virus infection.
Our laboratory uses a combination of cutting-edge cellular and molecular technologies to dissect and study virus-specific T cell responses to influenza and herpesviruses. These include techniques such as flow cytometry, cell sorting, PCR, RNAseq/ChiPseq and imaging.
Selected publications
- Jackson JT, Hu Y, Liu R, Masson F, D'Amico A, Carotta S, Xin A, Camilleri MJ, Mount AM, Kallies A, Wu L, Smyth GK, Nutt SL, Belz GT. Id2 expression delineates differential checkpoints in the genetic program of CD8α+ and CD103+ dendritic cell lineages. EMBO J. 2011 May 17;30(13):2690-704. PMID: 21587207
- Masson F, Kupresanin F, Mount A, Strasser A, Belz GT. Bid and Bim collaborate during induction of T cell death in persistent infection. J Immunol. 2011 186(7):4059-66. PMID: 21339359
- Belz GT, Kallies A. Effector and memory CD8+ T cell differentiation: toward a molecular understanding of fate determination. Curr Opin Immunol. 2010 Jun;22(3):279-85. PMID: 20434894
- Carotta S, Pang SH, Nutt SL, Belz GT. Identification of the earliest NK-cell precursor in the mouse BM. Blood. 2011 May 19;117(20):5449-52. PMID: 21422472
- Kallies A, Xin A, Belz GT, Nutt SL. Blimp-1 transcription factor is required for the differentiation of effector CD8+ T cells and memory responses. Immunity. 2009 21;31(2):283-95. PMID: 19664942
Research theme
Infectious diseases
Scientific discipline
- Immunology
Keywords
cytotoxic T cells, transcription factors, immunity, immune protection