Prof David Sansom

Research projects
David Sansom

Prof David Sansom

Chair in Transplant Immunology

Prof. David Samson

Contact

Professor David Sansom
Institute of Immunity and Transplantation
Department of Immunology
Royal Free Hospital
Rowland Hill Street
London NW3 2PF
UK
d.sansom [at] ucl.ac.uk
T. +44 (0)20 7794 0500  Ext. 22469

Research area

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.

Group members

Tie Zheng Hou
Daniel Janman
Alan Kennedy
Karen McGee
Blogoje Soskic

Recent publications

Hou, T.Z., O. Qureshi, C.J. Wang, J. Baker, S.P. Young, L.S. Walker, and D.M. Sansom, A Transendocytosis model of CTLA-4 function predicts its suppressive behaviour on regulatory T cells. Journal of Immunology, 2015. In Press.

Wang, C.J., F. Heuts, V. Ovcinnikovs, L. Wardzinski, C. Bowers, E.M. Schmidt, A. Kogimtzis, R. Kenefeck, D.M. Sansom, and L.S. Walker, CTLA-4 controls follicular helper T-cell differentiation by regulating the strength of CD28 engagement. Proc Natl Acad Sci U S A, 2014.

Soskic, B., O.S. Qureshi, T. Hou, and D.M. Sansom, A Transendocytosis Perspective on the CD28/CTLA-4 Pathway. Advances in immunology, 2014. 124: p. 95-136.

Schubert, D., C. Bode, R. Kenefeck, T.Z. Hou, J.B. Wing, A. Kennedy, A. et.al., S. Sakaguchi, L.S. Walker, D.M. Sansom, and B. Grimbacher, Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nature medicine, 2014. 20(12): p. 1410-1416.

Kenefeck, R., C.J. Wang, T. Kapadi, L. Wardzinski, K. Attridge, L.E. Clough, F. Heuts, A. Kogimtzis, S. Patel, M. Rosenthal, M. Ono, D.M. Sansom, P. Narendran, and L.S. Walker, Follicular helper T cell signature in type 1 diabetes. J Clin Invest, 2014.

Liaskou, E., L.E. Jeffery, P.J. Trivedi, G.M. Reynolds, S. Suresh, T. Bruns, D.H. Adams, D.M. Sansom, and G.M. Hirschfield, Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis. Gastroenterology, 2014. 147(1): p. 221-232 e7.

Gardner, D., L.E. Jeffery, and D.M. Sansom, Understanding the CD28/CTLA-4 (CD152) Pathway and Its Implications for Costimulatory Blockade. American Journal of Transplantation, 2014. 14(9): p. 1985-91.

Sansom, D.M. and L.S. Walker, CD28 costimulation: walking the immunological tightrope. European journal of immunology, 2013. 43(1): p. 42-5.

Kaur, S., O.S. Qureshi, and D.M. Sansom, Comparison of the intracellular trafficking itinerary of ctla-4 orthologues. PloS one, 2013. 8(4): p. e60903.

Dancer, R. and D.M. Sansom, Regulatory T cells and COPD. Thorax, 2013. 68(12): p. 1176-8.

Wang, C.J., R. Kenefeck, L. Wardzinski, K. Attridge, C. Manzotti, E.M. Schmidt, O.S. Qureshi, D.M. Sansom, and L.S. Walker, Cutting edge: cell-extrinsic immune regulation by CTLA-4 expressed on conventional T cells. Journal of immunology, 2012. 189(3): p. 1118-22.

Qureshi, O.S., S. Kaur, T.Z. Hou, L.E. Jeffery, N.S. Poulter, Z. Briggs, R. Kenefeck, A.K. Willox, S.J. Royle, J.Z. Rappoport, and D.M. Sansom, Constitutive clathrin-mediated endocytosis of CTLA-4 persists during T cell activation. The Journal of biological chemistry, 2012. 287(12): p. 9429-40.

Jeffery, L.E., A.M. Wood, O.S. Qureshi, T.Z. Hou, D. Gardner, Z. Briggs, S. Kaur, K. Raza, and D.M. Sansom, Availability of 25-Hydroxyvitamin D3 to APCs Controls the Balance between Regulatory and Inflammatory T Cell Responses. Journal of immunology, 2012. 189(11): p. 5155-64.

Walker, L.S. and D.M. Sansom, The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nature Reviews Immunology, 2011. 11(12): p. 852-63.

Qureshi, O.S., Y. Zheng, K. Nakamura, K. Attridge, C. Manzotti, E.M. Schmidt, J. Baker, L.E. Jeffery, S. Kaur, Z. Briggs, T.Z. Hou, C.E. Futter, G. Anderson, L.S. Walker, and D.M. Sansom, Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science, 2011. 332(6029): p. 600-3.

Older publications

Schmidt, E.M., C.J. Wang, G.A. Ryan, L.E. Clough, O.S. Qureshi, M. Goodall, A.K. Abbas, A.H. Sharpe, D.M. Sansom, and L.S. Walker, Ctla-4 controls regulatory T cell peripheral homeostasis and is required for suppression of pancreatic islet autoimmunity. J Immunol, 2009. 182(1): p. 274-82.

Jeffery, L.E., F. Burke, M. Mura, Y. Zheng, O.S. Qureshi, M. Hewison, L.S. Walker, D.A. Lammas, K. Raza, and D.M. Sansom, 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. Journal of immunology, 2009. 183(9): p. 5458-67.

Zheng, Y., C.N. Manzotti, F. Burke, L. Dussably, O. Qureshi, L.S. Walker, and D.M. Sansom, Acquisition of suppressive function by activated human CD4+ CD25- T cells is associated with the expression of CTLA-4 not FoxP3. Journal of immunology, 2008. 181(3): p. 1683-91.

Hewison, M., F. Burke, K.N. Evans, D.A. Lammas, D.M. Sansom, P. Liu, R.L. Modlin, and J.S. Adams, Extra-renal 25-hydroxyvitamin D3-1alpha-hydroxylase in human health and disease. J Steroid Biochem Mol Biol, 2007. 103(3-5): p. 316-21.

Sansom, D.M. and L.S. Walker, The role of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in regulatory T-cell biology. Immunol Rev, 2006. 212: p. 131-48.

Manzotti, C.N., M.K.P. Liu, F. Burke, L. Dussably, Y. Zheng, and D.M. Sansom, Integration of CD28 and CTLA-4 function results in differential responses of T cells to CD80 and CD86. Eur. J Immunol., 2006. 36: p. 1413-1422.

Mead, K.I., Y. Zheng, C.N. Manzotti, L.C. Perry, M.K. Liu, F. Burke, D.J. Powner, M.J. Wakelam, and D.M. Sansom, Exocytosis of CTLA-4 Is Dependent on Phospholipase D and ADP Ribosylation Factor-1 and Stimulated during Activation of Regulatory T Cells. J Immunol, 2005. 174(8): p. 4803-11.

Gough, S.C.L., L.S.K. Walker, and D.M. Sansom, CTLA4 gene polymorphism and autoimmunity. Immunological Reviews, 2005. 204: p. 102-115.

Zheng, Y., C.N. Manzotti, M. Liu, F. Burke, K.I. Mead, and D.M. Sansom, CD86 and CD80 Differentially Modulate the Suppressive Function of Human Regulatory T Cells. J Immunol, 2004. 172(5): p. 2778-84.

Somerset, D.A., Y. Zheng, M.D. Kilby, D.M. Sansom, and M.T. Drayson, Fast Track: Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset. Immunology, 2004. 112(1): p. 38-43.

Papageorgiou, A.C., M.D. Baker, J.D. McLeod, S.K. Goda, C.N. Manzotti, D.M. Sansom, H.S. Tranter, and K.R. Acharya, Identification of a secondary zinc-binding site in staphylococcal enterotoxin C2. Implications for superantigen recognition. J Biol Chem, 2004. 279(2): p. 1297-303.

Dussably, L.M., D.A. Somerset, M.D. Kilby, and D.M. Sansom, A role for regulatory T cells in materno-fetal tolerance. Fetal and Maternal Medicine Review, 2004. 15(4): p. 299-306.

Sansom, D.M., C.N. Manzotti, and Y. Zheng, What's the difference between CD80 and CD86? Trends Immunol, 2003. 24(6): p. 313-8.

Toellner, K.M., W.E. Jenkinson, D.R. Taylor, M. Khan, D.M. Sze, D.M. Sansom, C.G. Vinuesa, and I.C. MacLennan, Low-level hypermutation in T cell-independent germinal centers compared with high mutation rates associated with T cell-dependent germinal centers. J Exp Med, 2002. 195(3): p. 383-9.

Manzotti, C.N., H. Tipping, L.C.A. Perry, K.I. Mead, P.J. Blair, Y. Zheng, and D.M. Sansom, Inhibition of human T cell proliferation by CTLA-4 utilizes CD80 and requires CD25+ regulatory T cells. Eur J Immunol, 2002. 32(10): p. 2888-2896.

Sansom, D.M., CD28 , CTLA-4 and their ligands:who does what and to whom? Immunology, 2000. 101: p. 169-177.

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