Prof Peter Beverley
	Tel:	+44 (0) 1635 577 902
	E-mail:	peter.beverley@jenner.ac.uk
	Address:	The Jenner Building, Institute for Animal Health Compton, Newbury, Berkshire RG20 7NN
	Website:	www.jenner.ac.uk

Principal areas of research
Immunological memory, kinetics of T cells bearing HIV co-receptors, CD45 function.

Biography
Peter Beverley trained in medicine at University College London, qualifying in 1967. After registering he took up an MRC Junior Research Fellowship with Av Mitchison at the National Institute for Medical Research and then undertook a postdoctoral fellowship at Sloan Kettering Institute in New York with Lloyd Old and Ted Boyse. On returning to the UK in 1973 he joined the Imperial Cancer Research Fund Tumour Immunology Unit at University College London, becoming head in 1992. In 1988 he was awarded a personal chair. In 1995 he became Scientific Head of the Edward Jenner Institute for Vaccine Research at Compton, stepping down in 2005 to become a Principle Research Fellow in the Nuffield Department of Clinical Medicine at the University of Oxford. His research Group remains based in the Jenner building at Compton. He continues to do work on the mechanisms that maintain immunological memory.

Research
At Sloan Kettering I was part of a group that showed for the first time, using anti-Ly antisera, that there were different subsets (helper and suppressor/cytotoxic) of T lymphocytes. Later we showed that not only are there different subsets of lymphocytes with distinct phenotypes and functions but that naïve and memory T cells differ in their expression of CD45 isoforms, allowing their isolation and characterization. Present experiments continue to explore the function of different subsets of memory cells, seek to understand the function of CD45 isoforms and other cell surface molecules, and to unravel the mechanisms that maintain immunological memory.

In earlier work we showed using chromosomal markers that while naïve T cells are long lived, memory T cells turn over more rapidly. This led to studies using in vivo labeling with deuterated glucose to define the kinetics of human lymphocyte subpopulations and we have also investigated lymphocyte kinetics in EBV and HTLV1 infection. This has provided new insights into the host/virus interaction in HTLV1 infection. We are now using the methodology to define the kinetics of T cells bearing the HIV co-receptors CCR5 and CXCR4 in normal individuals and HIV patients, in order to understand better the pathogenesis of AIDS. We are also attempting to define the kinetics of CMV-antigen-specific populations to understand the effects of chronic antigen exposure on lymphocyte kinetics.

T cell memory consists of expanded clones of proliferating cells and we have therefore tried to understand what determines the size and longevity of clones. In early work we showed that during acute EBV infection there is massive clonal expansion. We also demonstrated that proliferative capacity is preserved by up-regulation of telomerase and lengthening of telomeres during the acute infection. We are now studying what happens during chronic CMV infection when very large clones are formed and come to take up a great deal of immunological space particularly in the elderly. We wish to know whether these clones shorten their telomeres, whether they continue to divide, whether they retain full immunological function and what is their influence on other immune responses, since it is known that CMV infection in the elderly is part of the immune risk phenotype that is correlated with poor survival.

We have shown that CD45 polymorphisms in humans can be a cause of severe combined immunodeficiency and are also associated with other diseases, so that CD45 functions as an immune response gene. We continue to study polymorphisms of CD45, trying to define the role of different isoforms in normal immune function and disease.

Key Publications
In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection. B. Asquith, Y. Zhang, A.J. Mosley, C.M. de Lara, D.L. Wallace, A. Worth, K. Lambrini, K. Meekings, G.E. Griffin, Y. Tanaka, D.F. Tough, P.C.L. Beverley, G.P. Taylor, D.C. Macallan, C.R.M. Bangham. Proc Nat. Acad. Sci. 104:8035-8040 (2007).

B Cell kinetics in humans: rapid turnover of peripheral blood memory cells. D.C. Macallan, D.L. Wallace, Y. Zhang, H. Ghattas, B. Asquith, C. De Lara, A. Worth, G. Panayiotakopoulos G.E. Griffin, D.F. Tough and P.C.L. Beverley. Blood 105: 3633-3640 (2005).

Virus-induced CD8+ T cell clonal expansion is associated with telomerase up-regulation and telomere length preservation: A mechanism for rescue from replicative senescence. M.K. Maini, M.V.D. Soares, C.F. Zilch, A.N. Akbar and P.C.L. Beverley. J. Immunol. 162: 4541-4546 (1999).

Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. A.N. Akbar, L. Terry, A. Timms, P.C.L. Beverley and G. Janossy. J. Immunol. 140: 1-8 (1988).

The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus.
A.G. Dalgleish, P.C.L. Beverley, P.R. Clapham, D.H. Crawford, M.F. Greaves and R.A. Weiss. Nature 312: 763 (1984).

Ly antigens as markers for functionally distinct subpopulations of thymus derived lymphocytes of the mouse. P. Kisielow, J.A. Hurst, H. Shiku, P.C.L. Beverley, M.K. Hoffman, E.A. Boyse and H.F. Oettgen. Nature 253: 219-220 (1975).

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