Professor Peter Lane PhD, MBChB, FRCP, FRCPath

Peter Lane

Institute of Immunology and Immunotherapy
Professor of Immunology

Contact details

Address
Institute of Immunology and Immunotherapy
MRC Centre for Immune Regulation
Institute for Biomedical Research
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Professor Peter Lane is interested in the molecular and cellular basis of CD4 memory and effector function, particularly in the context of human susceptibility to autoimmune disease. Acute and chronic autoimmune diseases are a huge burden to the NHS. Checkpoint inhibitors that suppress normal mechanisms that maintain self-tolerance, have been effective in revealing CD8 driven immune responses against cancers with high mutation loads, but at the cost of off target, primarily CD4 driven, autoimmunity which can be lethal. In his MRC funded research he has identified OX40 blockade as being effective in abrogating this “acute” inflammation without compromising anti-tumour immunity driven by CD8 T cells.

Unfortunately the work of Peter and his team has also shown that while blocking OX40-signals are effective in acute auto-inflammation, this strategy is ineffective in chronic autoimmunity, not because OX40-signals are not important, but because antibodies cannot target the OX40-signalling compartment which we think is occurring inside CD4 T cells.

Their recent work has identified the molecular control that directs this “cell intrinsic” OX40-signalling, which we have shown renders CD4 T cells resistant to being regulated, allowing failure of tolerance. Genome wide association studies in human autoimmunity combined with analysis of diseased tissue suggest this pathway is active in many human autoimmune diseases. Dissection of this pathway suggests strategies to treat human autoimmune disease without compromising basic immunity for health (minimal essential immune system) that is a common side effect of current immunosuppression.

Qualifications

  • FRCP, 2000
  • FRCPath (Immunology), 1997
  • PhD (Immunology), Birmingham, 1987
  • MRCPath (Immunology), 1987
  • MRCP, 1983
  • MBChB (Edinburgh), 1980

Biography

Peter qualified in medicine at Edinburgh University (1980). After training in hospital medicine (MRCP, 1983) he completed a PhD with Ian MacLennan funded by Wellcome Trust Clinical Fellowship (1987) and completed training in clinical immunology in 1987 (MRCPath).

Peter then spent two years in the USA working with Ed Clark and Jeff Ledbetter at the University of Washington, Seattle working on CD40 (key molecule for B cell activation) and CD28 (key molecule for T cell activation). This was followed by 6 years as a member at the Basel Institute for Immunology in Switzerland where he found activated T cells expressed a ligand for CD40, and that germinal centres, the sites of generation of high affinity antibodies and B cell memory were dependent on intact signals through CD28.

Peter returned to Birmingham in 1997, and has since pursued a career as a clinical academic with Programme Grant funding from both Wellcome Trust and MRC with a major interest in understanding the regulation of CD4 T cells.  

Teaching

Postgraduate supervision

  • Supervisor MRC Clinician Scientist Gwilym Webb (2015-  )
  • Supervisor Wellcome Trust Phd Emily Halford (2012-2016)

If you are interesting in studying any of these subject areas please contact Professor Peter Lane directly, or for any general doctoral research enquiries, please email mds-gradschool@contacts.bham.ac.uk.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

Research themes

T-cell biology, CD4 T-cell Tolerance and Immunity.

Research Activity

Overview

With Graham Anderson, our groups focus on the molecular and cellular basis of CD4 T cell responses in particular. Although are respective focuses are on the generation of tolerance in thymus versus protective CD4 responses in the periphery, it has been highly synergistic to have an integrated approach as tolerance and immunity go hand in hand. In particular it has been extremely fruitful to study the role of lymphoid tissue inducer cells in that are important for the generation of CD4 memory in secondary lymphoid organs, I thymus where they are implicated tolerance induction.

Key findings are:

  1. The critical role of the TNF receptors, OX40 and CD30 is CD4 effector and memory T cells
  2. The critical role of lymphoid tissue inducer cells in maintaining CD4 T cell memory
  3. The critical role of thymic lymphoid tissue inducer cells in the induction of AIRE in the embryonic thymus

Current funding:

  • MRC Programme Grant October, 2013-2018
  • Wellcome Trust Programme Grant 2007-2012

Other activities

  • Grant reviewer for MRC and EU bodies, ARUK and Wellcome Trust
  • Assesses patients with complex syndromes and autoimmunity and also patients with primary and secondary immunodeficiency, and allergy

Publications

Recent publications

Article

Nawaf, MG, Ulvmar, MH, Withers, DR, McConnell, FM, Gaspal, FM, Webb, GJ, Jones, ND, Yagita, H, Allison, JP & Lane, PJL 2017, 'Concurrent OX40 and CD30 ligand blockade abrogates the CD4-driven autoimmunity associated with CTLA4 and PD1 blockade while preserving excellent anti-CD8 tumor immunity', Journal of Immunology, vol. 199, no. 3, pp. 974-981. https://doi.org/10.4049/jimmunol.1700088

Webb, GJ, Hirschfield, GM & Lane, PJL 2016, 'OX40, OX40L and Autoimmunity: a Comprehensive Review', Clinical Reviews in Allergy & Immunology, vol. 50, pp. 312-332. https://doi.org/10.1007/s12016-015-8498-3

Cowan, JE, McCarthy, NI, Parnell, SM, White, AJ, Bacon, A, Serge, A, Irla, M, Lane, PJL, Jenkinson, EJ, Jenkinson, W & Anderson, G 2014, 'Differential requirement for CCR4 and CCR7 during the development of innate and adaptive αβT cells in the adult thymus', Journal of Immunology, vol. 193, no. 3, pp. 1204-12. https://doi.org/10.4049/jimmunol.1400993

Lane, PJL, McConnell, FM, Anderson, G, Nawaf, MG, Gaspal, FM & Withers, DR 2014, 'Evolving strategies for cancer and autoimmunity: back to the future', Frontiers in immunology, vol. 5, 154. https://doi.org/10.3389/fimmu.2014.00154

Anderson, G, Baik, S, Cowan, JE, Holland, AM, McCarthy, NI, Nakamura, K, Parnell, SM, White, AJ, Lane, PJL, Jenkinson, EJ & Jenkinson, WE 2014, 'Mechanisms of thymus medulla development and function', Current Topics in Microbiology and Immunology, vol. 373, pp. 19-47. https://doi.org/10.1007/82_2013_320

Nakamura, K, White, AJ, Parnell, SM, Lane, PJ, Jenkinson, EJ, Jenkinson, WE & Anderson, G 2013, 'Differential requirement for CCR4 in the maintenance but not establishment of the invariant Vγ5(+) dendritic epidermal T-cell pool', PLoS ONE, vol. 8, no. 9, pp. e74019. https://doi.org/10.1371/journal.pone.0074019

Baik, S, Jenkinson, EJ, Lane, PJL, Anderson, G & Jenkinson, W 2013, 'Generation of both cortical and Aire(+) medullary thymic epithelial compartments from CD205(+) progenitors', European Journal of Immunology, vol. 43, no. 3, pp. 589-94. https://doi.org/10.1002/eji.201243209

Cowan, JE, Parnell, SM, Nakamura, K, Caamano, JH, Lane, PJL, Jenkinson, EJ, Jenkinson, WE & Anderson, G 2013, 'The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development', The Journal of Experimental Medicine, vol. 210, no. 4, pp. 675-81. https://doi.org/10.1084/jem.20122070

Withers, DR, Gaspal, FM, Mackley, EC, Marriott, CL, Ross, EA, Desanti, GE, Roberts, NA, White, AJ, Flores-Langarica, A, McConnell, FM, Anderson, G & Lane, PJL 2012, 'Cutting edge: lymphoid tissue inducer cells maintain memory CD4 T cells within secondary lymphoid tissue', Journal of Immunology, vol. 189, no. 5, pp. 2094-8. https://doi.org/10.4049/jimmunol.1201639

Desanti, GE, Cowan, JE, Baik, S, Parnell, SM, White, AJ, Penninger, JM, Lane, PJL, Jenkinson, EJ, Jenkinson, W & Anderson, G 2012, 'Developmentally Regulated Availability of RANKL and CD40 Ligand Reveals Distinct Mechanisms of Fetal and Adult Cross-Talk in the Thymus Medulla', Journal of Immunology, vol. 189, no. 12, pp. 5519-26. https://doi.org/10.4049/jimmunol.1201815

Lane, P, Gaspal, F, McConnell, F, Kim, MY, Anderson, G & Withers, D 2012, 'Lymphoid tissue inducer cells: innate cells critical for CD4+ T cell memory responses?', Annals of the New York Academy of Sciences, vol. 1247, pp. 1-15. https://doi.org/10.1111/j.1749-6632.2011.06284.x

Lane, P, Gaspal, F, McConnell, F, Withers, D & Anderson, G 2012, 'Lymphoid tissue inducer cells: pivotal cells in the evolution of CD4 immunity and tolerance?', Frontiers in immunology, vol. 3, pp. 24. https://doi.org/10.3389/fimmu.2012.00024

Roberts, NA, White, A, Jenkinson, W, Turchinovich, G, Nakamura, K, Withers, D, McConnell, F, Desanti, G, Benezech, C, Parnell, SM, Cunningham, A, Paolino, M, Penninger, JM, Simon, AK, Nitta, T, Ohigashi, I, Takahama, Y, Caamano, J, Hayday, AC, Lane, P, Jenkinson, E & Anderson, G 2012, 'Rank Signaling Links the Development of Invariant γδ T Cell Progenitors and Aire(+) Medullary Epithelium.', Immunity, vol. 36, no. 3, pp. 427-437. https://doi.org/10.1016/j.immuni.2012.01.016

Gaspal, F, Withers, D, Saini, M, Bekiaris, V, McConnell, F, White, A, Khan, M, Yagita, H, Walker, L, Anderson, G & Lane, P 2011, 'Abrogation of CD30 and OX40 signals prevents autoimmune disease in FoxP3-deficient mice', The Journal of Experimental Medicine, vol. 208, no. 8, pp. 1579-1584. https://doi.org/10.1084/jem.20101484

Review article

Bevington, SL, Cauchy, P, Withers, DR, Lane, PJL & Cockerill, PN 2017, 'T cell receptor and cytokine signaling can function at different stages to establish and maintain transcriptional memory and enable T helper cell differentiation', Frontiers in immunology, vol. 8, 204. https://doi.org/10.3389/fimmu.2017.00204

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