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Effector and memory T cell subsets in man and mouse

English title Effector and memory T cell subsets in man and mouse
Applicant Sallusto Federica
Number 131092
Funding scheme Project funding (Div. I-III)
Research institution Istituto di Ricerca in Biomedicina (IRB)
Institution of higher education Università della Svizzera italiana - USI
Main discipline Immunology, Immunopathology
Start/End 01.07.2010 - 30.06.2013
Approved amount 672'302.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Clinical Immunology and Immunopathology

Keywords (3)

Memory T cells; Chemokine receptors; Human

Lay Summary (Italian)

Lead
I linfociti T effettori e della memoria immunologica
Lay summary

Questo progetto di ricerca si propone di studiare la differenziazione dei linfociti T e la memoria immunologica. Il progetto si divide in 3 parti. Nella prima parte si studia l'eterogeneità dei linfociti T effettori e della memoria, in particolare dei linfociti Th17 e Th22. Queste cellule sono responsabile della protezione contro funghi e batteri ma sono implicate anche in patologie autoimmuni, come la sclerosi multipla e la psoriasi. Nella seconda parte si studia il repertorio delle cellule T effettrici e della memoria specifiche per patogeni, vaccini o antigeni self. Questa analisi viene effettuata in donatori sani, in donatori vaccinati e in pazienti con sclerosi multipla. Nella terza parte si affrontano i meccanismi che controllano il traffico delle cellule T effettrici e della memoria per definire il ruolo dei recettori per le chemochine ed altri recettori che regolano la migrazione delle cellule T nei tessuti linfoidi e periferici e nelle diverse fasi della risposta immunitaria.

Direct link to Lay Summary Last update: 14.09.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
OMIP-018: chemokine receptor expression on human T helper cells.
Brodie Tess, Brenna Elena, Sallusto Federica (2013), OMIP-018: chemokine receptor expression on human T helper cells., in Cytometry. Part A : the journal of the International Society for Analytical Cytology, 83(6), 530-2.
Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype.
Baumjohann Dirk, Preite Silvia, Reboldi Andrea, Ronchi Francesca, Ansel K Mark, Lanzavecchia Antonio, Sallusto Federica (2013), Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype., in Immunity, 38(3), 596-605.
Memory T cells in latent Mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ Th1 subset.
Lindestam Arlehamn Cecilia S, Gerasimova Anna, Mele Federico, Henderson Ryan, Swann Justine, Greenbaum Jason A, Kim Yohan, Sidney John, James Eddie A, Taplitz Randy, McKinney Denise M, Kwok William W, Grey Howard, Sallusto Federica, Peters Bjoern, Sette Alessandro (2013), Memory T cells in latent Mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ Th1 subset., in PLoS pathogens, 9(1), 1003130-1003130.
Human Th17 subsets.
Sallusto Federica, Zielinski Christina E, Lanzavecchia Antonio (2012), Human Th17 subsets., in European journal of immunology, 42(9), 2215-20.
T-cell trafficking in the central nervous system.
Sallusto Federica, Impellizzieri Daniela, Basso Camilla, Laroni Alice, Uccelli Antonio, Lanzavecchia Antonio, Engelhardt Britta (2012), T-cell trafficking in the central nervous system., in Immunological reviews, 248(1), 216-27.
Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β.
Zielinski Christina E, Mele Federico, Aschenbrenner Dominik, Jarrossay David, Ronchi Francesca, Gattorno Marco, Monticelli Silvia, Lanzavecchia Antonio, Sallusto Federica (2012), Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β., in Nature, 484(7395), 514-8.
CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses
Chevalier N, Jarrossay D, Ho E, Avery DT, Ma CS, Yu D, Sallusto F, Tangye SG, Mackay CR (2011), CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses, in Journal of Immunology, 186(10), 5556-5568.
Dissecting the human immunologic memory for pathogens.
Zielinski Christina E, Corti Davide, Mele Federico, Pinto Dora, Lanzavecchia Antonio, Sallusto Federica (2011), Dissecting the human immunologic memory for pathogens., in Immunological reviews, 240(1), 40-51.

Collaboration

Group / person Country
Types of collaboration
Theodor Kocher Institute Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
University of Oxford Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
La Jolla Institute for Allergy and Immunology United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Giannina Gaslini Institute Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
University of Genoa Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Institute of Microbiology Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Cellular Therapy of Cancer Symposium 27.02.2013 London, UK
European Congress of Immunology 05.09.2012 Glasgow, Scotland
Cell Symposium "Human Immunity” 19.08.2012 Lisbon, Portugal
IL-17 and Related Cytokines: Basic Biology to Clinical Applications 18.06.2012 Dublin, Ireland


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Institute for Research in Biomedicine - Giornata delle Porte Aperte Italian-speaking Switzerland 25.05.2013

Awards

Title Year
EAACI Junior Poster Prize 2012
Member of EMBO 2011

Associated projects

Number Title Start Funding scheme
145038 Acquisition of a 2-Photon microscope for intravital analysis 01.12.2012 R'EQUIP
116440 Memory T cell subsets in man and mouse: identification, characterization and function 01.07.2007 Project funding (Div. I-III)
149475 Studies on T cell activation, differentiation and plasticity in humans 01.10.2013 Project funding (Div. I-III)
137127 ProDoc Cell Migration Research Module I: Immune cell migration in immunosurveillance and inflammation 01.10.2011 ProDoc

Abstract

The present proposal stems from my long-standing interest in T cell differentiation and immunological memory and deals with three major questions. The first question relates to the heterogeneity of effector and memory T cells with particular regard to the recently described Th17 and Th22 subsets. We will analyze flexibility and stability of human memory Th17 and Th22 cells and attempt to further dissect the heterogeneity of effector and memory T cells using surface markers and functional assays. We will also further investigate the requirement for Th17 and Th22 cell differentiation in humans and the role these cells play in autoimmune diseases such as multiple sclerosis and psoriasis. The second question relates to the repertoire of effector and memory T cell subsets and the dynamics of human immune response. Using a recently developed analytical method to study the antigenic specificity of human T cells, we will perform a systematic analysis of frequency, distribution, and fine specificity of antigen specific T cells in naïve, effector and memory T cell subsets, in particular in the Th17 and the recently described Th22 subsets. This analysis will be performed in healthy individuals, in vaccinated donors and in patients with multiple sclerosis. The third question relates to the mechanisms that control traffic of differentiated effector and memory T cells. Here we will address the role of chemokine receptors and other homing receptors in regulating migration both of naïve, effector and memory T cells at the induction phase in antigen-stimulated lymph nodes and at the effector phase in peripheral tissues. These experiments will be conducted in the mouse system taking advantage of gene-targeted animals and models of inflammatory diseases.
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