Clinical Immunology Unit
The Clinical Immunology Unit (UIC) is a translational research unit.
HIV/AIDS Immunopathogenesis is a main research area. HIV-2 apparently establishes a better equilibrium with the host than HIV-1, leading to a much slower rate of disease progression and lower levels of circulating virus. Current projects are mainly focused on the comparative study of these two infections as a strategy to clarify central issues in AIDS pathogenesis, taking advantage of the fact that Portugal is the only non-African country with a significant prevalence of HIV-2 infection.
Immune reconstitution is a critical research area for clinical practice. UIC’s investigation is centred on T-cell development in the thymus and T-cell homeostasis with special interest on the role of IL-7 as a major homeostatic cytokine. Several clinical settings are studied including immunodeficiencies, autoimmune diseases and transplantation.
A reference centre involving the UIC, the Hospital Santa Maria and the FMUL was recently created to provide diagnosis in primary immunodeficiencies, rare diseases that represent unique natural models to understand the immune system. A timely and precise diagnosis is essential for therapeutic success and genetic counselling, and constitutes a challenge for clinical immunologists. The UIC also provides diagnostic service in the area of immunoallergology, in parallel with investigation of mechanisms involved in drug allergy and induction of tolerance under specific immunotherapy.
» Research Areas
» Group Leader
» Research Team
Ana E. Sousa
MD (1986), Specialist in Internal Medicine (1994), and PhD (2000) in Clinical Immunology at the Faculty of Medicine, University of Lisbon.
Investigator / Assistant Professor at the Faculty of Medicine, University of Lisbon.
» Ongoing Research Projects
2007/10 - HIV-2 infection and the thymus. (FCT/PTDC/SAU-MII/66248/2006).
2007/10 - HIV/AIDS Program IMM-FCG. (Fundação Calouste Gulbenkian).
2008/10 - Cellular and Molecular Response of HIV-2 and HIV-1 Infection to Integration Modulation. Merck & Co., Inc..
2008/11 - Immune Reconstitution after Unrelated and Haplotype-Mismatched Stem Cell Transplantation. FCT. (PTDC/SAU-MII/67662/2006).
2009/11 - Long-term impact of thymectomy performed in early infancy. (PIC/IC/83068/2007).
2009/12 - Clinical implications of activation of PI3K/Akt signaling pathway in primary adult acute lymphoblastic leukemia. (PIC/IC/83023/2007).
2009/12 - Lymphoid Tissues in HIV-2 Infected patients. (PIC/IC/82712/2007).
2011/14- HIV/AIDS: contribute of naïve CD4 T cell homeostasis. FCT. (PTDC/SAU-MIC/109786/2009).
2011/13- Modulation of HIV replication and latency in human CD4 T cells by regulatory small RNAs. Merck Investigator Studies Program. (#39114).
2011/14- Cellular and molecular requirements in human regulatory T cell development. FCT. (PTDC/SAU-IMU/113541/2009).
» Science and Society Activities
Zvi Grossman (NIH, Bethesda, USA)
Jorge Carneiro (Instituto Gulbenkian de Ciência, Oeiras)
Remi Cheynier (Institut Pasteur, Paris)
Jeffrey Platt and Marilia Cascalho (Michigan University, Ann Arbor, USA)
Arne Akbar (University College, London)
Vasco Barreto (Instituto Gulbenkian de Ciência, Oeiras)
Carlos Tadokoro (Instituto Gulbenkian de Ciência, Oeiras)
Shohei Hori (RIKEN Research Center for Allergy and Immunology, Japan)
Visiting Art is a Project that results from an informal agreement between the UIC and and a private portuguese contemporary art collection.
The hall of the C wing of the third floor of the Egas Moniz building is visited sequentially by contemporary art pieces of this private collection for a few months - time to challenge investigators and visitors by their simple presence.
The current visiting works are from Angelo de Sousa, Carlos Augusto Ribeiro, Francisco Tropa, Jorge Martins, José Pedro Croft, Pedro Cabrita Reis and Nadir Afonso.
» Selected Publications
2012 NEDAI | MSD Award in Basic Research in Autoimmunity, NEDAI/Portuguese Society of Internal Medicine.
2008 Pfizer Award in Clinical Research, Lisbon Society of Medical Science.
2005 Bristol-Myers Squibb Research Award in Infection by virus of Human Immunodeficiency, Portuguese Association for AIDS Clinical Research (APECS).
2004 VIH Researches/ Glaxo-Smith Kline, Portuguese Society of Internal Medicine (SPMI).
2002 Dr. José Luís Champalimaud Award, Applied Research National, Commission of Fight Against AIDS.
» Useful Links
Albuquerque AS, Marques JG, Silva SL, Ligeiro D, Devlin BH, Dutrieux J, Cheynier R, Pignata C, Victorino RM, Markert ML, Sousa AE. (2012) Human FOXN1-Deficiency Is Associated with αβ Double-Negative and FoxP3+ T-Cell Expansions That Are Distinctly Modulated upon Thymic Transplantation. PLoS One 7:e37042.
Tendeiro R, Foxall RB, Baptista AP, Pinto F, Soares RS, Cavaleiro R, Valadas E, Gomes P, Victorino RM, Sousa AE. (2012) PD-1 and its ligand PD-L1 are progressively up-regulated on CD4 and CD8 T-cells in HIV-2 infection irrespective of the presence of viremia. AIDS 26:1065-1071.
Nunes-Cabaço H, Caramalho I, Sepúlveda N, Sousa AE. (2011) Differentiation of human thymic regulatory T-cells at the double positive stage. Eur J Immunol 41:3604-14.
Foxall RB, Albuquerque AS, Soares RS, Baptista AP, Cavaleiro R, Tendeiro R, Gomes P, Victorino RM, Sousa AE. (2011) Memory and naïve-like regulatory CD4+ T cells expand during HIV-2 infection in direct association with CD4+ T-cell depletion irrespectively of viremia. AIDS 25:1961-70.
Barbosa RR, Silva SP, Silva SL, Melo AC, Pedro E, Barbosa MP, Pereira-Santos MC, Victorino RM, Sousa AE. (2011) Primary B-Cell Deficiencies Reveal a Link between Human IL-17-Producing CD4 T-Cell Homeostasis and B-Cell Differentiation. PLoS One 6:e22848.
Soares RS, Tendeiro R, Foxall RB, Baptista AP, Cavaleiro R, Gomes P, Camacho R, Valadas E, Doroana M, Lucas M, Antunes F, Victorino RM, Sousa AE. (2011) Cell-associated viral burden provides evidence of ongoing viral replication in aviremic HIV-2-infected patients. J Virol 85: 2429-38.
Markert ML, Marques JG, Neven B, Devlin BH, McCarthy EA, Chinn IK, Albuquerque AS, Silva SL, Pignata C, de Saint Basile G, Victorino RM, Picard C, Debre M, Mahlaoui N, Fischer A, Sousa AE. (2011) First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases. Blood 117:688-96.
Nunes-Cabaço H, Ribot JC, Caramalho I, Serra-Caetano A, Silva-Santos B, Sousa AE. (2010) Foxp3 induction in human and murine thymus precedes the CD4+ CD8+ stage but requires early T-cell receptor expression. Immunol Cell Biol 88:523-8.
Cavaleiro R, Baptista AP., Soares RS, Tendeiro R, Foxall RB, Gomes P, Victorino RMM, Sousa AE. (2009) Major depletion of plasmacytoid dendritic cells in HIV-2 infection, an attenuated form of HIV disease. PloS Pathog 5:e1000667.
Azevedo RI, Soares MV, Barata JT, Tendeiro R, Serra-Caetano A, Victorino RM, Sousa AE. (2009) IL-7 sustains CD31 expression in human naive CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner. Blood 113:2999-3007.
Foxall RB, Cortesão CS, Albuquerque AS, Soares RS, Victorino RM, Sousa AE. (2008) Gag-specific CD4+ T-cell frequency is inversely correlated with proviral load and directly correlated with immune activation in infection with human immunodeficiency virus type 2 (HIV-2) but not HIV-1. J Virol 82:9795-9.
Pereira-Santos M.C., Baptista A.P., Melo A., Alves R.R., Soares R.S., Pedro E., Pereira-Barbosa M., Victorino R.M.M., Sousa A.E.. (2008) Expansion of circulating FoxP3+CD25bright CD4+ T cells during specific venom immunotherapy. Clin Exp Allergy 38:291-297.
A.S. Albuquerque, C.S. Cortesão, R.B. Foxall, R.S. Soares, R.M.M. Victorino, and A.E. Sousa. (2007) Rate of increase in circulating IL-7 and loss of IL-7R expression differ in HIV-1 and HIV-2 infections: two lymphopenic diseases with similar hyper immune-activation but distinct outcomes. J Immunol 178:3252-9.
Cavaleiro R., Brunn G.J., Albuquerque A.S., Victorino R.M.M., Platt J.L., and Sousa A.E.. (2007) Monocyte-mediated T-cell suppression by HIV-2 envelope proteins. Eur J Immunol 37:3435-44.
Gautier D., Beq S., Cortesão C.S., Sousa A.E., and Cheynier R.. (2007) Efficient thymopoiesis participates in the maintenance of peripheral CD4 T-cells during chronic HIV-2 infection. J Virol 80:12425-9.
Sousa, A. E., J. Carneiro, M. Meier-Schellersheim, Z. Grossman, and R. M. Victorino. (2002) CD4 T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2 but only indirectly to the viral load. J Immunol 169:3400-06.
Grossman, Z., M. Meier-Schellersheim, A. E. Sousa, R. M. Victorino, and W. E. Paul. (2002) CD4+ T-cell depletion in HIV infection: are we closer to understanding the cause? Nature Medicine 8:319-21.