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Alexandra M. Livingstone, Ph.D.

Alexandra M. Livingstone, Ph.D.

About Me

Faculty Appointments

Research Associate Professor - Department of Microbiology and Immunology (SMD)

Research Associate Professor - Center for Vaccine Biology and Immunology - Joint

Credentials

Education

PhD | UK-Cambridge U Med Sch. Immunology. 1983

BS | UK-U Edinburgh Fac Med. Molecular Biology. 1977

Research

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. Mic...
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.

Publications

Journal Articles

Are exercise and sitting time during chemotherapy for ovarian cancer associated with treatment-related side-effects, chemotherapy completion and survival?

Ross TL, Na R, Au-Yeung G, DeFazio A, Friedlander M, Sivakumaran T, Livingstone K, Nagle CM, O'Neill H, Williams M, Webb PM, Beesley VL

Gynecologic oncology.. 2024 November 190 :53-61. Epub 08/14/2024.

Wanted: A political sociology of race in Canada.

Livingstone AM

Canadian review of sociology = Revue canadienne de sociologie.. 2022 November 59 (4):557-559. Epub 11/02/2022.

CXCL10 peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter.

Prizant H, Patil N, Negatu S, Bala N, McGurk A, Leddon SA, Hughson A, McRae TD, Gao YR, Livingstone AM, Groom JR, Luster AD, Fowell DJ

Cell reports.. 2021 August 1036 (6):109523. Epub 1900 01 01.

TNF-Induced Interstitial Lung Disease in a Murine Arthritis Model: Accumulation of Activated Monocytes, Conventional Dendritic Cells, and CD21/CD23 B Cell Follicles Is Prevented with Anti-TNF Therapy.

Wu EK, Henkes ZI, McGowan B, Bell RD, Velez MJ, Livingstone AM, Ritchlin CT, Schwarz EM, Rahimi H

The Journal of immunology : official journal of the American Association of Immunologists.. 2019 December 1203 (11):2837-2849. Epub 10/28/2019.

Functional Immune Cell Differences Associated With Low Vaccine Responses in Infants.

Pichichero ME, Casey JR, Almudevar A, Basha S, Surendran N, Kaur R, Morris M, Livingstone AM, Mosmann TR

The Journal of infectious diseases.. 2016 June 15213 (12):2014-9. Epub 02/09/2016.

An animated landscape representation of CD4+ T-cell differentiation, variability, and plasticity: insights into the behavior of populations versus cells.

Rebhahn JA, Deng N, Sharma G, Livingstone AM, Huang S, Mosmann TR

European journal of immunology.. 2014 August 44 (8):2216-29. Epub 1900 01 01.

Modeling the dynamics and migratory pathways of virus-specific antibody-secreting cell populations in primary influenza infection.

Miao H, Sangster MY, Livingstone AM, Hilchey SP, Zhang L, Topham DJ, Mosmann TR, Holden-Wiltse J, Perelson AS, Wu H, Zand MS

PloS one.. 2014 9 (8):e104781. Epub 08/29/2014.

Modeling of influenza-specific CD8+ T cells during the primary response indicates that the spleen is a major source of effectors.

Wu H, Kumar A, Miao H, Holden-Wiltse J, Mosmann TR, Livingstone AM, Belz GT, Perelson AS, Zand MS, Topham DJ

The Journal of immunology : official journal of the American Association of Immunologists.. 2011 November 1187 (9):4474-82. Epub 09/23/2011.

Type I interferon supports primary CD8+ T-cell responses to peptide-pulsed dendritic cells in the absence of CD4+ T-cell help.

Ontiveros F, Wilson EB, Livingstone AM

Immunology.. 2011 April 132 (4):549-58. Epub 01/24/2011.

Unravelling the mechanisms of help for CD8+ T cell responses.

Livingstone AM, Wilson EB, Ontiveros F, Wang JC

Immunologic research.. 2009 December 45 (2-3):209-17. Epub 02/18/2009.

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.

Hilchey SP, Hyrien O, Mosmann TR, Livingstone AM, Friedberg JW, Young F, Fisher RI, Kelleher RJ, Bankert RB, Bernstein SH

Blood.. 2009 April 16113 (16):3809-12. Epub 02/04/2009.

Regulation of heat-induced apoptosis by Mcl-1 degradation and its inhibition by Hsp70.

Stankiewicz AR, Livingstone AM, Mohseni N, Mosser DD

Cell death and differentiation.. 2009 April 16 (4):638-47. Epub 01/16/2009.

Cutting edge: CD4+ T cell-derived IL-2 is essential for help-dependent primary CD8+ T cell responses.

Wilson EB, Livingstone AM

The Journal of immunology : official journal of the American Association of Immunologists.. 2008 December 1181 (11):7445-8. Epub 1900 01 01.

Dendritic cells: the immune information management experts.

Mosmann TR, Livingstone AM

Nature immunology.. 2004 June 5 (6):564-6. Epub 1900 01 01.

Cutting edge: CD4+ T cell help can be essential for primary CD8+ T cell responses in vivo.

Wang JC, Livingstone AM

The Journal of immunology : official journal of the American Association of Immunologists.. 2003 December 15171 (12):6339-43. Epub 1900 01 01.

Measuring the frequency of mouse and human cytotoxic T cells by the Lysispot assay: independent regulation of cytokine secretion and short-term killing.

Snyder JE, Bowers WJ, Livingstone AM, Lee FE, Federoff HJ, Mosmann TR

Nature medicine.. 2003 February 9 (2):231-5. Epub 01/21/2003.

Peptide-pulsed splenic dendritic cells prime long-lasting CD8(+) T cell memory in the absence of cross-priming by host APC.

Livingstone AM, Kuhn M

European journal of immunology.. 2002 January 32 (1):281-90. Epub 1900 01 01.

Dendritic cells need T cell help to prime cytotoxic T cell responses to strong antigens.

Livingstone AM, Kuhn M

European journal of immunology.. 1999 September 29 (9):2826-34. Epub 1900 01 01.

Translational control: a general mechanism for gene regulation during T cell activation.

Garcia-Sanz JA, Mikulits W, Livingstone A, Lefkovits I, Müllner EW

FASEB journal : official publication of the Federation of American Societies for Experimental Biology.. 1998 March 12 (3):299-306. Epub 1900 01 01.

Isolation of CD4+ and CD8+ T-Cell Clones from Mice Immunized with Synthetic Peptides on Splenic Dendritic Cells.

Livingstone A

Methods : a companion to Methods in enzymology.. 1996 June 9 (3):422-9. Epub 1900 01 01.

Antigen processing in populations of mature murine dendritic cells is caused by subsets of incompletely matured cells.

Koch F, Trockenbacher B, Kämpgen E, Grauer O, Stössel H, Livingstone AM, Schuler G, Romani N

The Journal of immunology : official journal of the American Association of Immunologists.. 1995 July 1155 (1):93-100. Epub 1900 01 01.

Presentation of antigen by mixed isotype class II molecules in normal H-2d mice.

Ruberti G, Sellins KS, Hill CM, Germain RN, Fathman CG, Livingstone A

The Journal of experimental medicine.. 1992 January 1175 (1):157-62. Epub 1900 01 01.

Proto-oncogene transcription after activation of Th-1 and Th-2 cells.

Morel PA, Walker JA, Livingstone AM, Tweardy DJ, Cairns JS

Annals of the New York Academy of Sciences.. 1991 December 30636 :386-9. Epub 1900 01 01.

Genetic dissection of T cell receptor V beta gene requirements for spontaneous murine diabetes.

Shizuru JA, Taylor-Edwards C, Livingstone A, Fathman CG

The Journal of experimental medicine.. 1991 September 1174 (3):633-8. Epub 1900 01 01.

The T cell receptor repertoire influences V beta element usage in response to myoglobin.

Ruberti G, Gaur A, Fathman CG, Livingstone AM

The Journal of experimental medicine.. 1991 July 1174 (1):83-92. Epub 1900 01 01.

Genetic analysis of diabetes in the nonobese diabetic mouse. I. MHC and T cell receptor beta gene expression.

Livingstone A, Edwards CT, Shizuru JA, Fathman CG

The Journal of immunology : official journal of the American Association of Immunologists.. 1991 January 15146 (2):529-34. Epub 1900 01 01.

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.

Ruberti G, Livingstone A, Danska JS, Gaur A, Fathman CG

Research in immunology. 1991 142 (5-6):491-3. Epub 1900 01 01.

Cim: an MHC class II-linked allelism affecting the antigenicity of a classical class I molecule for T lymphocytes.

Livingstone AM, Powis SJ, Günther E, Cramer DV, Howard JC, Butcher GW

Immunogenetics.. 1991 34 (3):157-63. Epub 1900 01 01.

The presumptive CDR3 regions of both T cell receptor alpha and beta chains determine T cell specificity for myoglobin peptides.

Danska JS, Livingstone AM, Paragas V, Ishihara T, Fathman CG

The Journal of experimental medicine.. 1990 July 1172 (1):27-33. Epub 1900 01 01.

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.

Livingstone AM, Powis SJ, Diamond AG, Butcher GW, Howard JC

The Journal of experimental medicine.. 1989 September 1170 (3):777-95. Epub 1900 01 01.

Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells.

Romani N, Koide S, Crowley M, Witmer-Pack M, Livingstone AM, Fathman CG, Inaba K, Steinman RM

The Journal of experimental medicine.. 1989 March 1169 (3):1169-78. Epub 1900 01 01.

Correlation of T cell receptor V beta gene family with MHC restriction.

Morel PA, Livingstone AM, Fathman CG

The Journal of experimental medicine.. 1987 August 1166 (2):583-8. Epub 1900 01 01.

The structure of T-cell epitopes.

Livingstone AM, Fathman CG

Annual review of immunology.. 1987 5 :477-501. Epub 1900 01 01.

Murine T cell clones.

Livingstone A, Fathman CG

Methods in enzymology.. 1987 150 :324-33. Epub 1900 01 01.

The specificity of responses against RT1.C antigens.

Stephenson, S.P.; Livingstone, A.M.; Howards, J.C.; Butcher, G.W.

Transplantation Proceedings. 1985; 17: 1844.

Recombination within the MHC can change the specificity of class I major transplantation antigens.

Livingstone, A.M.; Butcher, G.W.; Howard, J.C.

Transplantation Proceedings. 1983; 15: 1557.

The salvage and utilization of food waste for animal feeding.

STEPHEN J, LIVINGSTONE AM

Journal.. 1953 November 73 (6):675-92. Epub 1900 01 01.

Books

Molecular Mechanisms of Immunological Self-Recognition. (1993)

Chapter: T cells involved in inductive events in the pathogenesis of autoimmune diabetes mellitus.

Molecular Evolution of the Major Histocompatibility Complex. (1991)

Chapter: Antigen presentation by neoclassical MHC class I gene products in murine rodents.

The T Cell Receptor (1988)

Chapter: T Cell Structure/Function