Cellular Immunology Unit
The Cellular Immunology Unit studies mechanisms able to induce and maintain immune tolerance. We study diseases, or animal models of human pathologies, where the immune system has an inappropriate action, such as in autoimmunity, transplantation or allergy. We aim to reprogramme the immune system, inducing the expansion of regulatory T cells capable of reinstating the tolerance state. We always strive to validate our experimental results in collaboration with clinical scientists. Our results have led to several patents and to the formation of a start-up company: Acellera Therapeutics.
» Research Areas
» Group Leader
» Research Team
MD (1995) Faculty of Medicine, University of Lisbon
PhD (2002) in Immunology at the University of Oxford, UK
Post-doctoral research at the University of Oxford, UK, and at the University of Western Australia, Perth
Co-founder of the Start-up Acellera Therapeutics
Assistant Professor at the Faculty of Medicine, University of Lisbon
» Ongoing Research Projects
2009/11 - INTERREG IV B SUDOE Programa de Cooperação territorial Red de Inmunoterapia (INMUNONET – SOE1/P1/E014)
2007/09 - Co-receptor and co-stimulation blockade for the induction of regulatory T cells in allergic airways disease (FCT – PTDC/SAU-MII/64279/2006)
2009/11 Invariant Natural Killer T Cells in Allergic Asthma and Tolerogenic Therapy (FCT - PIC/IC/82895/2007).
2010/12 Tolerance induction to recombinant clotting factors in a murine model of hemophilia (PTDC/SAU-OSM/108267/2008) PI: Vanessa G Oliveira.
2011/13 Cellular therapy for liver-specific immune suppression (PTDC/SAU-TOX/114424/2009).
» Science and Society Activities
Juan J. Lafaille, Maria C. Lafaille (New York University, New York, USA)
Herman Waldmann (Sir William Dunn School of Pathology, University of Oxford, U.K.)
Ruy M. Ribeiro (Los Alamos National Laboratory, New Mexico, USA)
Florian Kreppel (University of Ulm, Germany)
João Eurico Fonseca (Unit of Reumathology Investigation, Instituto de Medicina Molecular, and Reumathology Service, Hospital de Santa Maria, Lisbon)
Bruno Silva Santos (Instituto de Medicina Molecular, Lisboa)
Long-standing collaboration with artist Marta de Menezes, who works at the interface of art and science and who has presented her work internationally.
Collaboration with artist Maria Manuela Lopes.
» Selected Publications
Prof. Heimburger Award in Coagulation Diseases, CSL Behring, 2009.
Idea to Product (I2P) Global Competition 2009, 2nd place, University of Texas at Austin, 2009.
BES National Innovation Award for Health Technologies, 2010.
Honorary mention in the ISCTE-IUL MIT-Portugal Venture Competition, 2010.
Young Entrepreneur Award 2010, from ANJE, 2010.
NEDAI Prize in Autoimmunity Research, 2011.
» Useful Links
Graça, L., Cobbold, S.P., Waldmann, H. (2002) Identification of regulatory T cells in tolerated allografts. Journal of Experimental Medicine, 195: 1641-1646.
Graça, L.*, Lin, C.-Y.*, Cobbold, S.P., Waldmann, H. (2002) Dominant transplantation tolerance impairs CD8+ T cell function but not expansion. Nature Immunology, 3: 1208-1213. (* Joint first authors)
Graça L, Le Moine A, Lin C-Y, Fairchild PJ, Cobbold SP, Waldmann H. (2004) Donor-specific transplantation tolerance: the paradoxial behavior of CD4+CD25+ T cells. Proceedings of the National Academy of Sciences USA 101: 10122-10126.
Duarte J, Agua-Doce A, Fonseca JE, Graça L. (2010) Modulation of synovial IL-17 and Foxp3 expression in the prevention of autoimmune arthritis. PLoS ONE. 5: e10558.
Monteiro M, Almeida CF, Caridade M, Ribot JC, Duarte J, Agua-Doce A, Wollenberg I, Silva-Santos B, Graça L. (2010) Identification of Regulatory Foxp3+ Invariant NKT Cells Induced by TGF-β. J Immunol. 185: 2157-2163.
Curotto de Lafaille MA, Lafaille JJ, Graca L. (2010) Mechanisms of tolerance and allergic sensitization in the airways and the lungs. Curr Opin Immunol. 22: 616-622.
Oliveira VG, Caridade M, Paiva RS, Demengeot J, Graca L. (2011). Sub-optimal CD4 T cell activation triggers autonomous TGF-β-dependent conversion to Foxp3+ regulatory T cells. Eur J Immunol. 41: 1249-1255.
Água-Doce A, Graca L. (2011) Prevention of house dust mite-induced allergic airways disease in mice through immune tolerance. PLoS ONE 6(7):e22320.
Wollenberg I, Agua-Doce A, Hernández A, Almeida C, Oliveira V, Faro J, Graça L. (2011) Regulation of germinal centre reaction by Foxp3+ follicular regulatory T cells. J Immunol. 187: 4553-4560.
Duarte J, Carrié N, Oliveira VG, Almeida C, Agua-Doce A, Rodrigues L, Simas P, Mars LT, Graca L. T cell apoptosis and induction of Foxp3+ regulatory T cells underlie the therapeutic efficacy of CD4-blockade in experimental autoimmune encephalomyelitis. J Immunol. 189:1680-1688.