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Alexandra Livingstone

TitleResearch Associate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentMicrobiology and Immunology
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 609
Rochester NY 14642
Other Positions
TitleResearch Associate Professor
InstitutionUniversity of Rochester Medical Center
DepartmentCenter for Vaccine Biology and Immunology

TitleResearch Associate Professor
InstitutionUniversity of Rochester Medical Center
DepartmentCancer Center

 
 Overview
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.

 
 Selected Publications
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  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. J Immunol. 2011 Nov 1; 187(9):4474-82.
    View in: PubMed
  2. 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.
    View in: PubMed
  3. Livingstone AM, Wilson EB, Ontiveros F, Wang JC. Unravelling the mechanisms of help for CD8+ T cell responses. Immunol Res. 2009 Dec; 45(2-3):209-17.
    View in: PubMed
  4. 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.
    View in: PubMed
  5. Wilson EB, Livingstone AM. Cutting edge: CD4+ T cell-derived IL-2 is essential for help-dependent primary CD8+ T cell responses. J Immunol. 2008 Dec 1; 181(11):7445-8.
    View in: PubMed
  6. Wonderlich J, Shearer G, Livingstone A, Brooks A. Induction and measurement of cytotoxic T lymphocyte activity. Curr Protoc Immunol. 2006 May; Chapter 3:Unit 3.11.
    View in: PubMed
  7. Mosmann TR, Livingstone AM. Dendritic cells: the immune information management experts. Nat Immunol. 2004 Jun; 5(6):564-6.
    View in: PubMed
  8. Wang JC, Livingstone AM. Cutting edge: CD4+ T cell help can be essential for primary CD8+ T cell responses in vivo. J Immunol. 2003 Dec 15; 171(12):6339-43.
    View in: PubMed
  9. 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. Nat Med. 2003 Feb; 9(2):231-5.
    View in: PubMed
  10. Livingstone AM, Kuhn M. Peptide-pulsed splenic dendritic cells prime long-lasting CD8(+) T cell memory in the absence of cross-priming by host APC. Eur J Immunol. 2002 Jan; 32(1):281-90.
    View in: PubMed
  11. Livingstone AM, Kuhn M. Dendritic cells need T cell help to prime cytotoxic T cell responses to strong antigens. Eur J Immunol. 1999 Sep; 29(9):2826-34.
    View in: PubMed
  12. Garcia-Sanz JA, Mikulits W, Livingstone A, Lefkovits I, Müllner EW. Translational control: a general mechanism for gene regulation during T cell activation. FASEB J. 1998 Mar; 12(3):299-306.
    View in: PubMed
  13. Koch F, Trockenbacher B, Kämpgen E, Grauer O, Stössel H, Livingstone AM, Schuler G, Romani N. Antigen processing in populations of mature murine dendritic cells is caused by subsets of incompletely matured cells. J Immunol. 1995 Jul 1; 155(1):93-100.
    View in: PubMed
  14. Ruberti G, Sellins KS, Hill CM, Germain RN, Fathman CG, Livingstone A. Presentation of antigen by mixed isotype class II molecules in normal H-2d mice. J Exp Med. 1992 Jan 1; 175(1):157-62.
    View in: PubMed
  15. Morel PA, Walker JA, Livingstone AM, Tweardy DJ, Cairns JS. Proto-oncogene transcription after activation of Th-1 and Th-2 cells. Ann N Y Acad Sci. 1991 Dec 30; 636:386-9.
    View in: PubMed
  16. Shizuru JA, Taylor-Edwards C, Livingstone A, Fathman CG. Genetic dissection of T cell receptor V beta gene requirements for spontaneous murine diabetes. J Exp Med. 1991 Sep 1; 174(3):633-8.
    View in: PubMed
  17. Ruberti G, Gaur A, Fathman CG, Livingstone AM. The T cell receptor repertoire influences V beta element usage in response to myoglobin. J Exp Med. 1991 Jul 1; 174(1):83-92.
    View in: PubMed
  18. Ruberti G, Livingstone A, Danska JS, Gaur A, Fathman CG. Analysis of the ternary complex of antigen, MHC and T-cell receptor: the influence of the T-cell receptor V beta repertoire on the V beta gene element usage. Res Immunol. 1991 Jun-Aug; 142(5-6):491-3.
    View in: PubMed
  19. Livingstone A, Edwards CT, Shizuru JA, Fathman CG. Genetic analysis of diabetes in the nonobese diabetic mouse. I. MHC and T cell receptor beta gene expression. J Immunol. 1991 Jan 15; 146(2):529-34.
    View in: PubMed
  20. Livingstone AM, Powis SJ, Günther E, Cramer DV, Howard JC, Butcher GW. Cim: an MHC class II-linked allelism affecting the antigenicity of a classical class I molecule for T lymphocytes. Immunogenetics. 1991; 34(3):157-63.
    View in: PubMed
  21. Danska JS, Livingstone AM, Paragas V, Ishihara T, Fathman CG. The presumptive CDR3 regions of both T cell receptor alpha and beta chains determine T cell specificity for myoglobin peptides. J Exp Med. 1990 Jul 1; 172(1):27-33.
    View in: PubMed
  22. Livingstone AM, Powis SJ, Diamond AG, Butcher GW, Howard JC. A trans-acting major histocompatibility complex-linked gene whose alleles determine gain and loss changes in the antigenic structure of a classical class I molecule. J Exp Med. 1989 Sep 1; 170(3):777-95.
    View in: PubMed
  23. Romani N, Koide S, Crowley M, Witmer-Pack M, Livingstone AM, Fathman CG, Inaba K, Steinman RM. Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells. J Exp Med. 1989 Mar 1; 169(3):1169-78.
    View in: PubMed
  24. Morel PA, Livingstone AM, Fathman CG. Correlation of T cell receptor V beta gene family with MHC restriction. J Exp Med. 1987 Aug 1; 166(2):583-8.
    View in: PubMed
  25. Livingstone A, Fathman CG. Murine T cell clones. Methods Enzymol. 1987; 150:324-33.
    View in: PubMed
  26. Livingstone AM, Fathman CG. The structure of T-cell epitopes. Annu Rev Immunol. 1987; 5:477-501.
    View in: PubMed

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