Theoretical immunology: in vivo lymphocyte dynamics

Principal investigator

Dr. Becca Asquith

Tel no............+44 (0) 207 594 3731
Fax no...........+44 (0) 207 402 0653

b.asquith@imperial.ac.uk

Background

I work on lymphocyte dynamics in vivo with a particular focus on the cytotoxic T lymphocyte response to the persistent retroviruses HIV-1 and HTLV-I. I use theoretical techniques (including mathematical modelling using ordinary differential equations and nonlinear regression) to interpret a wide range of experimental data.

Current Work

Ongoing projects include:

1.   Quantifying CTL killing of HIV-1 infected cells in vivo (in collaboration with Angela McLean, University of Oxford, UK).

2.   Understanding HIV-1 vaccine failure (in collaboration with Miles Davenport, UNSW, Australia).

3.   Quantifying aberrant lymphocyte dynamics in leukaemia (in collaboration with Luc Willems, FUSAG, Belgium).

4.   Understanding the virus-CTL interaction in HTLV-I infection (in collaboration with Charles Bangham, Imperial College, UK).

These projects are continuations of past work to quantify lymphocyte dynamics in humans in health [4,5] and disease [1,6] and in animal models of leukaemia [7,8]. And to quantify and model CTL control of HTLV-I and HIV-1 infection [2,3, 9-12].

Recent Key Publications (2000-present)

1. Asquith, B., Y. Zhang, A. Mosley, C. de Lara, D. Wallace, A. Worth, L. Kaftantzi, K. Meekings, G.E. Griffin, Y. Tanaka, D. Tough, P.C. Beverley, G.P. Taylor, D. Macallan, and C.R.M. Bangham, In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection. PNAS. 104(19):8035-8040. 2007  
2. Asquith, B. and A. McLean, 2007 In vivo CD8+ T Cell Killing of Immunodeficiency Virus-Infected Cells in Humans and Macaques. PNAS.  104(15):6365-6370. 2007  
3. Asquith, B., Edwards, C., Lipsitch, M. & McLean, A. R.  Inefficient CTL-mediated killing of HIV-1-infected cells in vivo. PLoS Biology. 4:0583-0592. 2006
4. Asquith, B., C. Debacq, D.C. Macallan, L. Willems, and C.R. Bangham, Lymphocyte kinetics: the interpretation of labelling data. Trends Immunol. 23(12): 596-601. 2002  
5. Macallan, D.C., B. Asquith, A.J. Irvine, D.L. Wallace, A. Worth, H. Ghattas, Y. Zhang, G.E. Griffin, D.F. Tough, and P.C. Beverley, Measurement and modeling of human T cell kinetics. Eur J Immunol. 33(8): 2316-26. 2003
6. Macallan, D.C., D.L. Wallace, A.J. Irvine, B. Asquith, A. Worth, H. Ghattas, Y. Zhang, G.E. Griffin, D.F. Tough, and P.C. Beverley, Rapid turnover of T cells in acute infectious mononucleosis. Eur J Immunol. 33(10): 2655-65. 2003
7. Debacq, C., B. Asquith, P. Kerkhofs, D. Portetelle, A. Burny, R. Kettmann, and L. Willems, Increased cell proliferation, but not reduced cell death, induces lymphocytosis in bovine leukemia virus-infected sheep. Proc Natl Acad Sci U S A. 99(15): 10048-10053. 2002
8. Debacq, C., B. Asquith, M. Reichert, A. Burny, R. Kettmann, and L. Willems, Reduced cell turnover in bovine leukemia virus-infected, persistently lymphocytotic cattle. J Virol. 77(24): 13073-83. 2003
9. Asquith, B. and C.R. Bangham, The role of cytotoxic T lymphocytes in human T-cell lymphotropic virus type 1 infection. J Theor Biol. 207(1): 65-79. 2000
10. Asquith, B. and C.R. Bangham, The dynamics of T-cell fratricide: application of a robust approach to mathematical modelling in immunology. J Theor Biol. 222(1): 53-69. 2003
11. Asquith, B., E. Hanon, G.P. Taylor, and C.R. Bangham, Is human T-cell lymphotropic virus type I really silent? Philos Trans R Soc Lond B Biol Sci. 355(1400): 1013-9. 2000
12. Asquith, B., A.J. Mosley, A. Barfield, S.E. Marshall, A. Heaps, P. Goon, E. Hanon, Y. Tanaka, G.P. Taylor, and C.R. Bangham, A functional CD8+ cell assay reveals individual variation in CD8+ cell antiviral efficacy and explains differences in human T-lymphotropic virus type 1 proviral load. J Gen Virol. 86(Pt 5): 1515-23. 2005