David Sansom

Professor of Transplant Immunology

Research area

Immune regulation.

Research programme

• Immune regulation

Research summary

The activation of T cells is a critical part of the immune response. Without effective T cell responses we could not fight off infections properly and vaccines would not work. However, T cell responses can also be dangerous to our bodies and it is clear that diseases such as rheumatoid arthritis and type-I diabetes as well as rejection of transplanted organs all involve unwanted T cell responses.

My laboratory works on fundamental aspects of how T cells determine whether to make immune responses or not. In particular we focus on the interplay between two receptors on T cells, CD28 and CTLA-4 and their binding partners, CD80 and CD86.  Our work on the underlying molecular and cellular mechanisms has led to advances in understanding how the CD28/CTLA-4 system functions and this knowledge has been used to develop tests of human T cell function and regulatory T cell suppression.

Patient involvement

We work closely with clinical colleagues performing research aimed at identifying gene mutations that cause immune dysregulation. This involves primary immune deficiencies, where we have worked on understanding CTLA-4 deficiency.  Using blood cells from patients and unique experimental approaches we have identified regulatory T cell defects in CTLA-4-deficient patients.  We are also interested in developing functional approaches to study more complex (auto)immune problems, for example in disorders such as arthritis and transplant rejection.

Publications

Selected publications

• Rowshanravan B, Halliday N, Sansom DM. CTLA-4: a moving target in immunotherapy. Blood. 2017;pii:blood-2017-06-741033
• Jeffery LE, Henley P, Marium N, Filer A, Sansom DM, Hewison M, Raza K. Decreased sensitivity to 1,25-dihydroxyvitamin D3 in T cells from the rheumatoid joint. J Autoimmun. 2017;pii: S0896-8411:30420-1
• Verma N, Burns SO, Walker LSK, Sansom DM. Immune deficiency and autoimmunity in patients with CTLA-4 (CD152) mutations. Clin Exp Immunol. 2017;190:1-7
• Davies EG, Cheung M, Gilmour K, Maimaris J, Curry J, Furmanski A, Sebire N, Halliday N, Mengrelis K, Adams S, Bernatoniene J, Bremner R, Browning M, Devlin B, Erichsen HC, Gaspar HB, Hutchison L, Ip W, Ifversen M, Leahy TR, McCarthy E, Moshous D, Neuling K, Pac M, Papadopol A, Parsley KL, Poliani L, Ricciardelli I, Sansom DM, Voor T, Worth A, Crompton T, Markert ML, Thrasher AJ. Thymus transplantation for complete DiGeorge syndrome: European experience. J Allergy Clin Immunol. 2017;140:1660-1670.e16
• Hou TZ, Verma N, Wanders J, Kennedy A, Soskic B, Janman D, Halliday N, Rowshanravan B, Worth A, Qasim W, Baxendale H, Stauss H, Seneviratne S, Neth O, Olbrich P, Hambleton S, Arkwright PD, Burns SO, Walker LS, Sansom DM. Identifying functional defects in patients with immune dysregulation due to LRBA and CTLA-4 mutations. Blood. 2017;129:1458-1468
• Navarini AA, Hruz P, Berger CT, Hou TZ, Schwab C, Gabrysch A, Higgins R, Frede N, Padberg Sgier BC, Kämpe O, Burgener AV, Marquardsen F, Baldin F, Bigler M, Kistner A, Jauch A, Bignucolo O, Meyer B, Meienberg F, Mehling M, Jeker LT, Heijnen I, Daikeler TD, Gebbers JO, Grimbacher B, Sansom DM, Jeker R, Hess C, Recher M. Vedolizumab as a successful treatment of CTLA-4-associated autoimmune enterocolitis. J Allergy Clin Immunol. 2017;139:1043-1046.e5
• Douthwaite J, Moisan J, Privezentzev C, Soskic B, Sabbah S, Cohen S, Collinson A, England E, Huntington C, Kemp B, Zhuang L, Hudak S, Rees DG, Goldberg D, Barton C, Chang L, Vainshtein I, Liang M, Iciek L, Ambery P, Peakman M, Vaughan TJ, Tree TI, Sansom DM, Bowen MA, Minter RR, Jermutus L. A CD80-Biased CTLA4-Ig Fusion Protein with Superior In Vivo Efficacy by Simultaneous Engineering of Affinity, Selectivity, Stability, and FcRn Binding. J Immunol. 2017;198:528-537
• Gardner DH, Jeffery LE, Soskic B, Briggs Z, Hou TZ, Raza K, Sansom DM. 1,25(OH)2D3 Promotes the Efficacy of CD28 Costimulation Blockade by Abatacept. J Immunol. 2015;195:2657-65
• Sansom DM. IMMUNOLOGY. Moving CTLA-4 from the trash to recycling. Science. 2015;349:377-8.

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