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.
2016 Jun 15
Pichichero ME, Casey JR, Almudevar A, Basha S, Surendran N, Kaur R, Morris M, Livingstone AM, Mosmann TR. "Functional Immune Cell Differences Associated With Low Vaccine Responses in Infants." The Journal of infectious diseases. 2016 Jun 15; 213(12):2014-9. Epub 2016 Feb 09. |
2014 Aug
Rebhahn JA, Deng N, Sharma G, Livingstone AM, Huang S, Mosmann TR. "An animated landscape representation of CD4+ T-cell differentiation, variability, and plasticity: insights into the behavior of populations versus cells." European journal of immunology. 2014 Aug; 44(8):2216-29. |
2014
Miao H, Sangster MY, Livingstone AM, Hilchey SP, Zhang L, Topham DJ, Mosmann TR, Holden-Wiltse J, Perelson AS, Wu H, Zand MS. "Modeling the dynamics and migratory pathways of virus-specific antibody-secreting cell populations in primary influenza infection." PloS one. 2014 9(8):e104781. Epub 2014 Aug 29. |
2011 Nov 1
Wu H, Kumar A, Miao H, Holden-Wiltse J, Mosmann TR, Livingstone AM, Belz GT, Perelson AS, Zand MS, Topham DJ. "Modeling of influenza-specific CD8+ T cells during the primary response indicates that the spleen is a major source of effectors." The Journal of immunology : official journal of the American Association of Immunologists. 2011 Nov 1; 187(9):4474-82. Epub 2011 Sep 23. |
2011 Apr
Ontiveros F, Wilson EB, Livingstone AM. "Type I interferon supports primary CD8+ T-cell responses to peptide-pulsed dendritic cells in the absence of CD4+ T-cell help." Immunology. 2011 Apr; 132(4):549-58. Epub 2011 Jan 24. |
