Ana Espada de Sousa Lab

Ana Espada de Sousa

Group Leader

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Human Immunodeficiency and Immune Reconstitution

Ana Espada de Sousa’s Lab investigates the mechanisms that regulate human immunity, with a core focus on T-cell homeostasis, particularly CD4 T cells, the main orchestrators of the immune system.

In parallel to fundamental research, clinical settings are used to investigate human immunodeficiency, namely the role of inborn errors of immunity (IEI) and HIV/AIDS immunopathogenesis, through the study of HIV-2 infection, a naturally attenuated form of HIV disease.

Research is structured around four main axes:

T cell development in the human thymus:

T cells committed to the regulatory lineage in the thymus (Tregs) are essential for immune homeostasis and self-tolerance. We use a multiomics approach to investigate their differentiation trajectories and functional heterogeneity including both CD4 and CD8 Tregs, using thymic tissue removed during routine cardiac surgery.

Human naïve CD4 T cell biology:

T cells egress the thymus as naïve cells essential to generate responses against new pathogens, vaccines and tumours throughout life. By following a cohort of adults who underwent total thymectomy in infancy, the group investigates how the immune system adapts to the long-term absence of thymic renewal.

HIV/AIDS immunopathogenesis (HIV-1 and HIV-2):

HIV-2 establishes a unique equilibrium with the host, leading to a much slower rate of CD4 decline than HIV-1, and reduced circulating viruses despite persistent viral reservoirs. The laboratory investigates the protective responses induced by HIV-2 in the gut and lymph nodes to uncover new targets to control persistent infections and related inflammation. Portugal has the highest prevalence of HIV-2 outside Africa, making these studies particularly relevant.

Immunodeficiency due to inborn errors of immunity (IEI):

The laboratory studies susceptibility to chronic inflammation, autoimmunity, and cancer (specifically gastric cancer) in these “natural models” providing insights into human immune regulation. The group collaborates with the National Health Service (SNS) to deliver advanced diagnostic testing and specialized follow-up through participation in a dedicated academic centre for these rare diseases.

2026-2027: Mapping HIV-2 lymph nodes to learn how to control HIV-1. Principal Investigator: Ana Espada de Sousa. Funding Agency: Gilead Genesis.

2026-2027: Landscape and specificity of the T cell repertoire in gastritis of patients with common variable immune deficiency. Principal Investigator: Margarida Rei. Funding Agency: Fundação para a Ciência e a Tecnologia.

2021-2025: NAIVETALENT – Targeting naïve CD4 T cells to avoid human immunodeficiency. Principal Investigator: Ana Espada de Sousa. Funding Agency: Fundação para a Ciência e a Tecnologia.

Fernandes SM, Farias GB, Pires AR, Santos DF, Antão AV, Pires A, Moura R, Godinho-Santos A, Marques RT, Mc Gomes A, Ferreira C, Nunes-Cabaço H, Gomes P, Poças J, Vasconcelos C, Badura R, Sousa AE. (2026) Lymph node remodelling underlies the attenuated form of HIV/AIDS in people with HIV-2. J Infect. 2026 Jun;92(6):106760. doi: 10.1016/j.jinf.2026.106760.

Badura R, Martins NC, Farias GB, Tendeiro R, Foxall RB, Santos DF, Gomes AMC, Marques RT, Moleirinho B, Godinho-Santos AC, Valadas E, Gomes P, Almeida ARM, Sousa AE. (2026) Shaping the founders: naïve CD4 T cell heterogeneity in people with HIV-1 or HIV-2. Front Immunol. 2026 May 11;17:1810186. doi: 10.3389/fimmu.2026.1810186.

Junginger ZI, Adameck R, Raposo AASF, Rosmaninho P, Sousa AE, Almeida ARM. (2026) A Cell-Intrinsic Role for RANK in Regulatory T Cells of the Human Thymus. Eur J Immunol. 2026 Feb;56(2):e70132. doi: 10.1002/eji.70132.

Torres-Valle A, et al.; EuroFlow Consortium. (2026) Immunologic biomarkers of noninfectious complications and overall survival in common variable immunodeficiency. J Allergy Clin Immunol. 2026 Feb;157(2):454-469. doi: 10.1016/j.jaci.2025.10.020.

B. Moleirinho, M. Paulo-Pedro, N. C. Martins, E. Jelagat, E. Conti, T. R. Velho, M. Abecasis, R. Anjos, A. R. M. Almeida, A. E. Sousa (2025). A backbone-based flow cytometry approach to decipher regulatory T cell trajectories in the human thymus. Frontiers in Immunology 16: 1553535. doi: 10.3389/fimmu.2025.1553535.

M. Paulo-Pedro, B. Moleirinho, D. F. Santos, A. M. C. Gomes, M. Rei, A. R. M. Almeida, J. G. Marques, S. L. Silva, A. E. Sousa (2025). Adulthood outcomes of thymic transplantation in a case of congenital athymia due to FOXN1mutation. Journal of Allergy and Clinical Immunology. doi: 10.1016/j.jaci.2025.02.006.

A. A. S. F. Raposo, P. Rosmaninho, S. L. Silva, S. Paço, M. E. Brazão, A. Godinho-Santos, Y. Tokunaga-Mizoro, H. Nunes-Cabaço, A. Serra-Caetano, A. R. M. Almeida, A. E. Sousa (2024). Decoding mutational hotspots in human disease through the gene modules governing thymic regulatory T cells. Frontiers in Immunology 15: 1458581. doi: 10.3389/fimmu.2024.1458581.

H. Nunes-Cabaço, A. Ramalho-Dos-Santos, A. R. Pires, L. R. Martins, J. T. Barata, A. E. Sousa (2022). Human CD4 T cells from thymus and cord blood are convertible into CD8 T cells by IL-4. Frontiers in Immunology 13: 834033. doi: 10.3389/fimmu.2022.834033.

Z. Grossman, N. J. Singh, F. R. Simonetti, M. M. Lederman, D. C. Douek, S. G. Deeks, T. Kawabe, G. Bocharov, M. Meier-Schellersheim, H. Alon, N. Chomont, Z. Grossman, A. E. Sousa, M. Margolis, F. Maldarelli (2020). ‘Rinse and replace’: boosting T cell turnover to reduce HIV-1 reservoirs. Trends in Immunology. doi: 10.1016/j.it.2020.04.003.

S. M. Fernandes, A. R. Pires, P. Matoso, C. Ferreira, H. Nunes-Cabaço, L. Correia, E. Valadas, J. Poças, P. Pacheco, H. Veiga-Fernandes, R. B. Foxall, A. E. Sousa (2018). HIV-2 infection is associated with preserved GALT homeostasis and epithelial integrity despite ongoing mucosal viral replication. Mucosal Immunology 11(1): 236–248.

A. J. Amaral, J. Andrade, R. B. Foxall, P. Matoso, A. M. Matos, R. S. Soares, C. Rocha, C. G. Ramos, R. Tendeiro, A. Serra-Caetano, J. A. Guerra-Assunção, M. Santa-Marta, J. Gonçalves, M. Gama-Carvalho, A. E. Sousa (2017). miRNA profiling of human naïve CD4 T cells links miR-34c-5p to cell activation and HIV replication. The EMBO Journal 36(3): 346–360.

I. Caramalho, V. Nunes-Silva, A. R. Pires, C. Mota, A. I. Pinto, H. Nunes-Cabaço, R. B. Foxall, A. E. Sousa (2015). Human regulatory T-cell development is dictated by interleukin-2 and -15 expressed in a non-overlapping pattern in the thymus. Journal of Autoimmunity 56: 98–110.

R. I. Azevedo, M. V. Soares, J. T. Barata, R. Tendeiro, A. Serra-Caetano, R. M. Victorino, A. E. Sousa (2009). IL-7 sustains CD31 expression in human naïve CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner. Blood 113: 2999–3007.

A. E. Sousa, J. Carneiro, M. Meier-Schellersheim, Z. Grossman, 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. Journal of Immunology 169: 3400–3406.

Z. Grossman, M. Meier-Schellersheim, A. E. Sousa, R. M. Victorino, W. E. Paul (2002). CD4+ T-cell depletion in HIV infection: are we closer to understanding the cause? Nature Medicine 8: 319–323.

A complete list of publications can be found here.

2019: Prémio de Investigação em Autoimunidade NEDAI, SPMI

2015: Prémio NEDAI de Investigação Básica em Autoimunidade, SPMI

2012: Prémio NEDAI de Investigação Básica em AutoImunidade, SPMI

2008: Prémio Pfizer de Investigação Clínica, SCML

2005: Prémio de Investigação Bristol-Myers Squibb em Infecção por VIH, APECS

2004: AMI – Saúde / Doenças Infecciosas e Parasitárias (Menção Honrosa), AMI

2004: VIH – Glaxo-Smith Kline, SPMI

2003: Prémio LabMed Saúde

2002: Prémio Dr. José Luís Champalimaud – Investigação aplicada, DGS

2002: Prémio Dr. José Luís Champalimaud – Investigação Básica (Menção Honrosa), DGS

1998: Prémio Pfizer (Menção Honrosa), SCML