Luís Graça Lab

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

• Immune tolerance
• Regulatory T cells
• Autoimmunity
• Vaccines
• Allergy
• Transplantation
• Antibodies
• Germinal Centers

Ongoing Research Projects

2020/2023 Thymic Abnormalities in Rare Immunological Diseases. Coordinator: Luís Graça. Funding Agency: Fundação para a Ciência e a Tecnologia/European Joint Programme on Rare Diseases (EU).

2020/2021 Nanomateriais para desenho de novas vacinas. Coordinator: Luís Graça. Funding Agency: Fundação para a Ciência e a Tecnologia.

2020/2021 Immune senescence in COVID-19. Coordinator: Luís Graça. Funding Agency: Fundação para a Ciência e a Tecnologia.

Awards

2019 Professor Jorge Silva Horta (second prize).

2018 Carregosa Bank - Ordem dos Médicos (honorable mention).

2017 iMM Innovators, TwinToInfect.

2011 NEDAI Prize in Autoimmunity Research.

2010 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.

2009 Idea to Product (I2P) Global Competition 2009, 2nd place, University of Texas at Austin.

2009 Prof. Heimburger Award in Coagulation Diseases, CSL Behring.

Selected Publications

Malato, J., Ribeiro, R.M., Fernandes E., Leite, P.P., Casaca, P., Carlos Antunes, Válter R Fonseca, Antunes, C., Fonseca, V.R., Gomes, M.C., and Graca, L. (2023). Stability of hybrid versus vaccine immunity against BA.5 infection over 8 months. Lancet Infect Dis. DOI:https://doi.org/10.1016/S1473-3099(22)00833-7

Malato, J., Ribeiro, R.M., Leite, P.P., Casaca, P., Fernandes, E., Antunes, C., Fonseca, V.R., Gomes, M.C., and Graca, L. (2022). Risk of BA.5 infection among persons exposed to previous SARS-CoV-2 variants. N. Engl. J. Med. 387, 953–954.

Kumar S, Fonseca VR, Ribeiro F, Basto AP, Água-Doce A, Monteiro M, Elessa D, Miragaia RJ, Gomes T, Piaggio E, Segura E, Gama-Carvalho M, Teichmann SA, Graça L (2021). Developmental bifurcation of human T follicular regulatory cells. Science Immunology 6(59): eabd8411. (Full Text)

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)

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