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

2023/2026 Modulation of human antibody responses by T follicular helper subsets. Coordinator: Luís Graça. Funding Agency: Fundação para a Ciência e a Tecnologia (Lisbon, PT).

2023/2025 Reconstructing immune dysregulation leading to therapeutic resistance in Crohn’s disease. Coordinator: Luís Graça. Funding Agency: Merck Sharp and Dohme (Rahway, NJ, US).

2022/2025 Harnessing germinal centre regulation for improved vaccines. Coordinator: Luís Graça. Funding Agency: "la Caixa" Foundation (Barcelona, ES).

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 (Lisbon, PT).

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

Awards

2023 Pfizer Award in Clinical Research; Pfizer / Sociedade das Ciências Médicas de Lisboa.

2023 Medal of Merit from the Alvalade Municipality.

2019 Research Excellence Award. Caixa Geral de Depósitos / University of Lisbon.

2017 iMM Innovators, TwinToInfect.

2011 NEDAI Prize in Autoimmunity Research.

2010 Young Entrepreneur Award 2010, National Society of Entrepreneurship (ANJE).

2010 National Innovation Award for Health Technologies; Espirito Santo Bank (BES).

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

Graca L, Faria AC, Ribeiro RM (2023) Illuminating a blind spot of SARS-CoV-2 immunity. Nature Immunol. 10.1038/s41590-034-01518-w

Graca L, Jacobsen J, Kumar S (2023) The expanding family of T follicular regulatory cells. Sci Immunol 8:eadg7526.

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.

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.

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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