Research Bio
The generation of immunological memory is essential for protection against subsequent infections. My lab works on CD8+ T cell memory. We have developed model systems for generating long-lasting CD8+ T cell memory under conditions where the antigen is unlikely to persist for more than a few days. Mice are immunised with dendritic cells pulsed with peptides defining class I epitopes; memory is evaluated by cytokine production or cytotoxicity after in vitro restimulation with antigen. CD8+ T cell priming in this system is entirely dependent on CD4+ T cell help, but does not require B cells or antibody. Mice immunised with peptide-pulsed DC show peptide-specific memory cytotoxic responses more than a year after immunisation; in contrast, protective memory declines quite sharply 8-15 days after immunisation. We are currently testing whether this is due to death of antigen-specific cells, or to their reversion to a less activated state in the absence of antigen.
Until recently, research on memory has depended on functional assays that measure memory responses at the population level. It is now possible, however, to identify antigen-specific cells using techniques that don't rely on functional assays (TCR-transgenics, MHC-peptide tetramers); in addition, the frequency of antigen-specific cells can be estimated using single cell assays for cytokine production (flow cytometry, elispots) that are very much more sensitive than limiting dilution analysis for CTL precursors. We are now combining these techniques with the DC immunisation protocol to ask basic questions about the behaviour of CD8+ memory T cells, to design successful vaccination strategies against the relevant pathogens.
2009 Apr 16
Hilchey SP, Hyrien O, Mosmann TR, Livingstone AM, Friedberg JW, Young F, Fisher RI, Kelleher RJ, Bankert RB, Bernstein SH. "Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a "vaccinal effect" of rituximab." Blood. 2009 Apr 16; 113(16):3809-12. Epub 2009 Feb 04. |
2009
Livingstone AM, Wilson EB, Ontiveros F, Wang JC. "Unravelling the mechanisms of help for CD8+ T cell responses." Immunologic research. 2009 45(2-3):209-17. Epub 2009 Feb 18. |
2008
Wilson EB, Livingstone AM. "Cutting edge: CD4+ T cell-derived IL-2 is essential for help-dependent primary CD8+ T cell responses." The Journal of immunology : official journal of the American Association of Immunologists. 2008 181(11):7445-8. |
2004 Jun
Mosmann TR, Livingstone AM. "Dendritic cells: the immune information management experts." Nature immunology. 2004 Jun; 5(6):564-6. |
2003 Feb
Snyder JE, Bowers WJ, Livingstone AM, Lee FE, Federoff HJ, Mosmann TR. "Measuring the frequency of mouse and human cytotoxic T cells by the Lysispot assay: independent regulation of cytokine secretion and short-term killing." Nature medicine. 2003 Feb; 9(2):231-5. Epub 2003 Jan 21. |
