Lymphocyte Regulation
The Cellular Immunology Lab 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 reprogram 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.
Research Team
Research Areas
- Tolerance
- Regulatory T cells
- Autoimmunity
- Allergy
- Transplantation
- Monoclonal antibodies
- Animal models
Ongoing Research Projects
2015/2019 Informatics and Genomics of Helper T cells (ENLIGHT-TEN-MSCA-ITN-2015-675395 - H2020)
2015/2018 Multidisciplinary Strategy to Develop Novel Multicomponent Nanoscale Systems for Immune Modulation (UTAP-ICDT/DTP-FTO/0016/2014)
2015/2017 Regulação das respostas dos centros germinativos em doentes alérgicos (HMSP-ICT/0034/2013)
Awards
- Professor Jorge Silva Horta (second prize), 2019.
- Carregosa Bank - Ordem dos Médicos (honorable mention), 2018.
- iMM Innovators, TwinToInfect, 2017.
- NEDAI Prize in Autoimmunity Research, 2011.
- Young Entrepreneur Award 2010, from ANJE, 2010.
- Honorary mention in the ISCTE-IUL MIT-Portugal Venture Competition, 2010.
- BES National Innovation Award for Health Technologies, 2010.
- Idea to Product (I2P) Global Competition 2009, 2nd place, University of Texas at Austin, 2009.
- Prof. Heimburger Award in Coagulation Diseases, CSL Behring, 2009.
Selected Publications
- Deng J, Wei Y, Fonseca VR, Graca L*, Yu D* (2019) “Follicular helper and follicular regulatory T cells in autoimmune rheumatic diseases: phenotype, pathogenesis and targeted immunotherapies”. Nature Rev Rheumatol. In press. (* joint senior/corresponding authors)
- Fonseca VR, Romão VC, Agua-Doce A, Santos M, López-Presa D, Ferreiras AC, Fonseca JE, Graca L (2018) “The Ratio of Blood T Follicular Regulatory Cells to T Follicular Helper Cells Marks Ectopic Lymphoid Structure Formation While Activated Follicular Helper T Cells Indicate Disease Activity in Primary Sjögren's Syndrome”. Arthritis Rheumatol. 70:774-784.
- Fonseca VR, Agua-Doce A, Maceiras AR, Pierson W, Ribeiro F, Romão VC, Pires AR, Silva SL, Fonseca JE, Sousa AE, Linterman MA, Graca L (2017) Human blood CXCR5+Foxp3+ T cells are indicators of ongoing humoral activity not fully licensed with suppressive function. Science Immunol. 2, eaan1487.
- Maceiras R, Almeida SCP, Mariotti-Ferrandiz E, Chaara W, Jebbawi F, Six A, Hori S, Klatzmann D, Faro J, Graca L (2017) T follicular helper and T follicular regulatory cells from the same germinal centers have different TCR-specificity. Nature Commun. 8:15067.
- Monteiro M, Agua-Doce A, Almeida CF, Fonseca-Pereira D, Veiga-Fernandes H, Graca L (2015) IL-9 expression by invariante NKT cells is not imprinted during thymic development. J Immunol. 195: 3463-3471.
- Oliveira VG, Agua-Doce A, Curotto de Lafaille M, Lafaille JJ, Graca L. (2013) Adjuvant facilitates anti-CD4 mediated immune tolerance to recombinant factor VIII in hemophilia through a Foxp3-independent mechanism that relies on IL-10. Blood 121: 3938-3945.
- Monteiro M, Almeida CF, Agua-Doce A, Graca L. (2013) Induced IL-17-producing invariant Natural Killer T cells require activation in presence of TGF-β. J Immunol 190: 805-811.
- Duarte J, Carrié N, Oliveira VG, Almeida C, Agua-Doce A, Rodrigues L, Simas P, Mars LT, Graca L. (2012) 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.
- Wollenberg I, Agua-Doce A, Hernández A, Almeida C, Oliveira V, Faro J, Graca L. (2011) Regulation of germinal centre reaction by Foxp3+ follicular regulatory T cells. J Immunol 187: 4553-4560. (380 citations – report on the discovery of Tfr cells)
- Oliveira VG, Paiva R, Demengeot J, Graca L. (2011) Sub-optimal CD4 T cell activation triggers TGF-β-dependent conversion to Foxp3+ regulatory T cells Eur J Immunol 41:1249-55.