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Dr Maja Wållberg PhD

Dr Maja Wållberg, PhD

Immunology

Autoimmunity

Type 1 diabetes

Immune tolerance

Islet transplantation


Research Interests

I am a group leader in  the Department of Pathology investigating pathways for restoring immune tolerance to beta cells in models of type 1 diabetes. I am interested in processes that lead to the destruction of beta cells in type 1 diabetes, and I have used many different approaches to do that. Recently, I have described in detail how immunomodulating treatment with anti-CD3 antibodies changes the properties of islet-specific effector T cells, finding that one of the most important changes is a downregulation of their cellular metabolism (Wallberg et al. Immunology, 2017). My own results and the increased interest in immunometabolism in the field of immunology inspired me to investigate the effects of hyperglycemia on T cell mediated immune responses, and our first paper on this has recently been published (Recino et al. 2017). It is an acknowledged fact that people with diabetes have higher levels of certain infections, but the mechanisms that contribute to this are incompletely investigated. Glucose levels have been reported to influence the effector qualities of anti-tumour and anti-inflammatory T cell responses, but we find that in vivo hyperglycemia affects neither acute CTL proliferation, killing or interferon gamma production. However, our most recent results indicate that hyperglycemia may affect the formation of long term immunological memory responses.

In order to better investigate events in the islet, we have developed a method for non-invasive in vivo multiphoton imaging of immune events in grafted islets in collaboration with Paul Garside, Jim Brewer and Robert Benson at the University of Glasgow. We are also investigating immunological barriers to the succeful restoration of insulin production through gene therapy in collaboration with Professor Roy Calne, The Dick White Referrals Clinic and the University of Singapore.

Keywords

cytotoxicity ; FOXP3 ; animal models ; autoimmunity ; helper T cells ; B cells ; T cell differentiation ; activation ; metabolism ; NOD mice ; fluorescence microscopy ; TGF-beta ; CTL ; islet ; regulatory T cells ; dendritic cells ; immune tolerance ; memory cells ; inflammation

Topics

  • type I diabetes
  • autoimmunity
  • neuroimmunology

Key Publications

Recino, A., Barkan, K., Ladds, G., Cooke, A., Wong, F. S. and Wallberg, M., Hyperglycemia does not affect antigen specific activation and cytolytic killing by CD8+ T cells in vivo. Biosci Rep 2017.

Wallberg, M., Recino, A., Phillips, J., Howie, D., Vienne, M., Paluch, C., Azuma, M., Wong, F. S., Waldmann, H. and Cooke, A., Anti-CD3 treatment up-regulates programmed cell death protein-1 expression on activated effector T cells and severely impairs their inflammatory capacity. Immunology 2017.

Barbera Betancourt A, Emery JL, Recino A, Wong FS, Cooke A, Okkenhaug K, Wållberg M. Inhibition of Phosphoinositide 3-Kinase p110delta Does Not Affect T Cell Driven Development of Type 1 Diabetes Despite Significant Effects on Cytokine Production PLOS One, January 19, 2016

Wallberg, M and Cooke, A. Immune Mechanisms in type 1 diabetes. Trends in Immunology 2013 Dec 34(12):583-91

Thomas DC, Wong FS, Zaccone P, Green EA, Wållberg M. Protection of islet grafts through transforming growth factor-β-induced tolerogenic dendritic cells. Diabetes. 2013 Sep;62(9):3132-42. 

Wållberg M, Wong FS, Green EA. An islet-specific pulse of TGF-β abrogates CTL function and promotes β cell survival independent of Foxp3+ T cells. J Immunol. 2011 Feb 15;186(4):2543-51.

Wållberg M, Green EA. Are B cells a potential target for therapeutic intervention in the classical T cell-mediated autoimmune disease type 1 diabetes? Inflamm Allergy Drug Targets. 2009 Jun;8(2):130-8.

Brodie GM, Wållberg M,  Santamaria P, Wong FS, Green EA. B-cells promote intra-islet CD8+ cytotoxic T-cell survival to enhance type 1 diabetes. Diabetes. 2008 Apr;57(4):909-17. Epub 2008 Jan 9.

Wållberg M, Bergquist J, Achour A, Breij E, Harris RA. Malondialdehyde modification of myelin oligodendrocyte glycoprotein leads to increased immunogenicity and encephalitogenicity. Eur J Immunol. 2007 Jul;37(7):1986-95.

Chamberlain G, Wållberg M, Rainbow D, Hunter K, Wicker LS, Green EA. A 20-Mb region of chromosome 4 controls TNF-alpha-mediated CD8+ T cell aggression toward beta cells in type 1 diabetes. J Immunol. 2006 Oct 15;177(8):5105-14.

Other Publications

De Riva, A., Wallberg, M., Ronchi, F., Coulson, R., Sage, A., Thorne, L., Goodfellow, I., McCoy, K. D., Azuma, M., Cooke, A. and Busch, R., Regulation of type 1 diabetes development and B-cell activation in nonobese diabetic mice by early life exposure to a diabetogenic environment. PLoS One 2017. 12: e0181964

Thaker, Y. R., Recino, A., Raab, M., Jabeen, A., Wallberg, M., Fernandez, N. and Rudd, C. E., Activated Cdc42-associated kinase 1 (ACK1) binds the SAM domain of adaptor SLP-76 and phosphorylates proximal tyrosines. J Biol Chem 2017.

Pratigya Gautam, Asha Recino, Robert D Foale, Jing Zhao,Shu Uin Gan, Maja Wållberg, Roy Calne, Andrew M.L Lever. Promoter Optimisation of Lentiviral Vectors for Efficient Insulin Gene Expression in Canine Mesenchymal Stromal Cells: Potential Surrogate Beta Cells Journal of Gene Medicine, in press   

Wållberg M, Bergquist J, Achour A, Breij E and Harris RA. Malondialdehyde modification of Myelin Oligodendrocyte Glycoprotein leads to increased immunogenicity and encephalitogenicity. European Journal of Immunology 2007 Jul;37(7):1986-95

Wållberg M and Harris RA. Coinfection with Trypanosoma brucei brucei prevents experimental autoimmune encephalomyelitis in DBA/1 mice through induction of suppressor APC. International immunology 2005 Jun 17(6): 721-8

Wållberg M, Wefer J and Harris RA. Vaccination with myelin oligodendrocyte glycoprotein adsorbed to alum effectively protects DBA/1 mice from experimental autoimmune encephalomyelitis.  European Journal of Immunology 2003 6:1539-1547