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Human Integrative Immunology

Leader:

Fernando A. Arosa, Ph.D.

Major interests

The way scientists envision Immunology is changing and a comprehensive dissection of the mechanisms that control the life span and differentiation of T cells is essential to understand their function in health and disease. Our research activities aim at:

1. Elucidating the molecular mechanisms regulating cell growth, survival and differentiation of human CD8+ T cells by environmental signals, such as those provided by the g-common cytokine IL-15 and novel erythrocyte derived growth and survival factors, and how they impact on the expression of Killer Immunoglobulin-like Receptors (KIR).
2. Understanding why cell surface MHC class I molecules have a tendency to become free-heavy chains and form homotypic/heterotypic associations as well as elucidating the role of these "new" cell surface structures in the regulation of cell-cell communication and function, for instance through interactions with KIR.
To achieve these aims we use in vitro culture of primary human T cells in combination with advance flow cytometry, immunofluorescence and biochemistry techniques. Overall, these studies may help unveiling novel aspects of the biology of T cells that, in turn, may allow the development of new therapeutic strategies for the treatment of diseases where the immunological system is malfunctioning either by defect (e.g. cancer) or by excess (e.g. autoimmunity).

Research Team

Name	Position	Contact
Fernando A. Arosa	Assistant professor	fernando.arosa@iscsn.cespu.pt
Elsa M. Cardoso	Assistant Professor	elsa.cardoso@iscsn.cespu.pt
Ana Sofia Botelho	Adjunct professor	sofia.botelho@iscsn.cespu.pt
Isabel Baldaia	Marter student

 

Relevant Publications (selected from a total of 30)

1. Antunes RF, Brandão C, Maia M, Arosa FA (2010). Human red blood cells secrete a novel cell growth and survival factor for normal and malignant T cells. Immunol. Cell Biol. (in press).
 
2. Correia MP, Cardoso EM, Pereira CF, Neves R, Uhrberg M, Arosa FA (2009). Hepatocytes and IL-15: a favorable microenvironment for CD8+ T cell survival and differentiation. J. Immunol.  182:6149-59.
 
3. Antunes RF, Brandão C, Carvalho G, Girão C, Arosa FA (2009). Red blood cells carry out T cell growth and survival bioactivities that are sensitive to cyclosporine A.  Cell Mol Life Sci 66:3387-98.
 
4. Arosa FA, Santos SG, Powis SJ (2007). Open conformers: the hidden face of MHC-I molecules. Trends Immunol 28:115-23.
 
5. Santos SG, Antoniou A, Powis SJ, Arosa FA (2006). Lack of tyrosine 320 impairs spontaneous endocytosis and enhances release of HLA-B27 molecules. J. Immunol. 176:2942-9.
 
6. Stewart CA, Laugier-Anfossi F, Vely F,Saulquin X, Riedmuller J, Tisserant A, Gauthier L, Romagné F, Ferracci G, Arosa FA, Moretta A, Sun PD, Ugolini S, Vivier E (2005). Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors. Proc. Natl. Acad. Sci. USA. 102:13224-9.
 
7. Santos SG, Powis SJ, Arosa FA (2004). Misfolding of MHC-class I molecules in activated T cells allows cis-interactions with receptors and signaling molecules and is associated with tyrosine phosphorylation. J. Biol. Chem. 279:53062-70.
 
8. Alves NM, Hooibrink B, Arosa FA, van Lier RAW (2003). IL-15 induces antigen-independent expansion and differentiation of human naive CD8+ T cells in vitro. Blood 102:2541-6.
 
9. Fonseca AM, Porto G, Uchida K, Arosa FA. (2001). Red blood cells inhibit activation induced cell death and oxidative stress in human peripheral blood T lymphocytes. Blood 97:3152-60.
 
10. Arosa FA, de Jesus O, Porto G, Carmo AM, de Sousa M. (1999). Calreticulin is expressed on the cell surface of activated human peripheral blood T lymphocytes in association with major histocompatibility complex class I molecules. J. Biol. Chem. 274:16917-22.

Projects

Project Title: Immunomodulatory properties of transfusional blood units
Funding entity: CESPU, CRL
Project identification: 03‐GBMC‐CICS‐10
Period covered: from 01-01-2010 to 31-12-2011
PI: Fernando A. Arosa
 
Project Title: Cytokine profile of IL-15-diferentiated human CD8+ T cells
Funding entity: CESPU, CRL
Project identification: 02‐GBMC‐CICS‐09
Period covered: from 01-01-2009 to 31-12-2010
PI: Elsa M. Cardoso