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Università della Svizzera italiana

Activin-A co-opts IRF4 and AhR signaling to induce human regulatory T cells that restrain asthmatic responses

Tousa, Sofia ; Semitekolou, Maria ; Morianos, Ioannis ; Banos, Aggelos ; Trochoutsou, Aikaterini I. ; Brodie, Tess M. ; Poulos, Nikolaos ; Samitas, Konstantinos ; Kapasa, Maria ; Konstantopoulos, Dimitris ; Paraskevopoulos, Giannis ; Gaga, Mina ; Hawrylowicz, Catherine M. ; Sallusto, Federica ; Xanthou, Georgina

In: Proceedings of the national academy of sciences of the United States of America, 2017, vol. 114, no. 14, p. E2891-E2900

Type 1 regulatory T (Tr1) cells play a pivotal role in restraining human T-cell responses toward environmental allergens and protecting against allergic diseases. Still, the precise molecular cues that underlie their transcriptional and functional specification remain elusive. Here, we show that the cytokine activin-A instructs the generation of CD4+ T cells that express the...

Università della Svizzera italiana

Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals

Corti, Davide ; Langedijk, Johannes P. M. ; Hinz, Andreas ; Seaman, Michael S. ; Vanzetta, Fabrizia ; Fernandez-Rodriguez, Blanca M. ; Silacci, Chiara ; Pinna, Debora ; Jarrossay, David ; Balla-Jhagjhoorsingh, Sunita ; Willems, Betty ; Zekveld, Maria J. ; Dreja ; O’Sullivan, Eithne ; Pade, Corinna ; Orkin, Chloe ; Jeffs, Simon A. ; Montefiori, David C. ; David, Davis ; Weissenhorn, Winfried ; McKnight, Aine ; Heeney, Jonathan L. ; Sallusto, Federica ; Sattentau, Quentin J. ; Weiss, robin A. ; Lanzavecchia, Antonio

In: Plos one, 2010, vol. 5, no. 1, p. e8805

Background The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. Methods and Findings We immortalized IgG+ memory B cells from individuals infected with...

Università della Svizzera italiana

Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies

Kabanovaa, Anna ; Perez, Laurent ; Lilleri, Daniele ; Marcandalli, Jessica ; Agatic, Gloria ; Becattini, Simone ; Preite, Silvia ; Fuschillo, Dario ; Percivalle,Elena ; Sallusto, Federica ; Gerna, Giuseppe ; Corti, Davide ; Lanzavecchia, Antonio

In: Proceedings of the national academy of sciences of the United States of America, 2014, vol. 111, no. 50, p. 17965-17970

The use of neutralizing antibodies to identify the most effective antigen has been proposed as a strategy to design vaccines capable of eliciting protective B-cell immunity. In this study, we analyzed the human antibody response to cytomegalovirus (human cytomegalovirus, HCMV) infection and found that antibodies to glycoprotein (g)B, a surface glycoprotein that has been developed as a HCMV...

Università della Svizzera italiana

An anti-HIV-1 V3 loop antibody fully protects cross-clade and elicits T-cell immunity in macaques mucosally challenged with an R5 clade C SHIV

Watkins, Jennifer D. ; Siddappa, Nagadenahalli B. ; Lakhashe, Samir K. ; Humbert, Michael ; Sholukh, Anton ; Hemashettar, Girish ; Wong, Yin Ling ; Yoon, John K. ; Wang, Wendy ; Novembre, Francis J. ; Villinger, Francois ; Ibegbu, Chris ; Patel, Kalpana ; Corti, Davide ; Agatic, Gloria ; Vanzetta, Fabrizio ; Bianchi, Siro ; Heeney, Jonathan L. ; Sallusto, Federica ; Lanzavecchia, Antonio ; Ruprecht, Ruth M.

In: Plos one, 2011, vol. 6, no. 3, p. e18207

Neutralizing antibodies have been shown to protect macaques against SHIV challenge. However, genetically diverse HIV-1 clades have evolved, and a key question left unanswered is whether neutralizing antibodies can confer cross-clade protection in vivo. The novel human monoclonal antibody HGN194 was isolated from an individual infected with an HIV-1 clade AG recombinant circulating recombinant...

Università della Svizzera italiana

CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function

Rivino, Laura ; Gruarin, Paola ; Häringer, Barbara ; Steinfelder, Svenja ; Lozza, Laura ; Steckel, Bodo ; Weick, Anja ; Sugliano, Elisa ; Jarrossay, David ; Kühl, Anja A. ; Loddenkemper, Christoph ; Abrignani, Sergio ; Sallusto, Federica ; Lanzavecchia, Antonio ; Geginat, Jens

In: Journal of experimental medicine, 2010, vol. 207, no. 3, p. 565-577

Interleukin (IL)-10 produced by regulatory T cell subsets is important for the prevention of autoimmunity and immunopathology, but little is known about the phenotype and function of IL-10–producing memory T cells. Human CD4+CCR6+ memory T cells contained comparable numbers of IL-17– and IL-10–producing cells, and CCR6 was induced under both Th17-promoting conditions and upon tolerogenic...

Università della Svizzera italiana

Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma

Jacquelot, Nicolas ; Enot, David P. ; Flament, Caroline ; Vimond, Nadège ; Blattner, Carolin ; Pitt, Jonathan M. ; Yamazaki, Takahiro ; Roberti, María Paula ; Daillère, Romain ; Vétizou, Marie ; Poirier-Colame, Vichnou ; Semeraro, Michaëla ; Caignard, Anne ; Slingluff Jr., Craig L. ; Sallusto, Federica ; Rusakiewicz, Sylvie ; Weide, Benjamin ; Marabelle, Aurélien ; Kohrt, Holbrook ; Dalle, Stéphane ; Cavalcanti, Andréa ; Kroemer, Guido ; Di Giacomo, Anna Maria ; Maio, Michele ; Wong, Phillip ; Yuan, Jianda ; Wolchok, Jedd ; Umansky, Viktor ; Eggermont, Alexander ; Zitvogel, Laurence

In: The journal of clinical investigation, 2016, vol. 126, no. 3, p. 921-937

Melanoma prognosis is dictated by tumor-infiltrating lymphocytes, the migratory and functional behavior of which is guided by chemokine or cytokine gradients. Here, we retrospectively analyzed the expression patterns of 9 homing receptors (CCR/CXCR) in naive and memory CD4+ and CD8+ T lymphocytes in 57 patients with metastatic melanoma (MMel) with various sites of metastases to evaluate...

Università della Svizzera italiana

Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41

Sabin, Charles ; Corti, Davide ; Buzon, Victor ; Seaman, Mike S. ; Hulsik, David Lutje ; Hinz, Andreas ; Vanzetta, Fabrizia ; Agatic, Gloria ; Silacci, Chiara ; Mainetti, Lara ; Scarlatti, Gabriella ; Sallusto, Federica ; Weiss, Robin ; Lanzavecchia, Antonio ; Weissenhorn, Winfried

In: Plos pathogens, 2010, vol. 6, no. 11, p. e1001195

The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 A° resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a...

Università della Svizzera italiana

Fetal human cytomegalovirus transmission correlates with delayed maternal antibodies to gH/gL/pUL128-130-131 complex during primary infection

Lilleri, Daniele ; Kabanova, Anna ; Revello, Maria Grazia ; Percivalle, Elena ; Sarasini, Antonella ; Genini, Emilia ; Sallusto, Federica ; Lanzavecchia, Antonio ; Corti, Davide ; Gerna, Giuseppe

In: Plos one, 2013, vol. 8, no. 3, p. e59863

Primary human cytomegalovirus (HCMV) infections during pregnancy are associated with a high risk of virus transmission to the fetus. To identify correlates of intrauterine HCMV transmission, serial serum samples from HCMV transmitter and non-transmitter pregnant women with primary HCMV infection were analyzed for the presence of neutralizing antibodies against different glycoproteins and...

Università della Svizzera italiana

Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine

Corti, Davide ; Suguitan Jr., Amorsolo ; Pinna, Debora ; Silacci, Chiara ; Fernandez-Rodriguez, Blanca M. ; Vanzetta, Fabrizia ; Santos, Celia ; Luke, Catherine J. ; Torres-Velez, Fernando J. ; Temperton, Nigel J. ; Weiss, Robin A. ; Sallusto, Federica ; Subbarao, Kanta ; Lanzavecchia, Antonio

In: The Journal of clinical investigation, 2010, vol. 120, no. 5, p. 1663-1673

The target of neutralizing antibodies that protect against influenza virus infection is the viral protein HA. Genetic and antigenic variation in HA has been used to classify influenza viruses into subtypes (H1–H16). The neutralizing antibody response to influenza virus is thought to be specific for a few antigenically related isolates within a given subtype. However, while heterosubtypic...

Università della Svizzera italiana

Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23

Markle, Janet G. ; Martínez-Barricarte, Rubén ; Ma, Cindy S. ; Deenick, Elissa K. ; Ramírez-Alejo, Noé ; Mele, Federico ; Latorre, Daniela ; Mahdaviani, Seyed Alireza ; Aytekin, Caner ; Mansouri, Davood ; Bryant, Vanessa L. ; Jabot-Hanin, Fabienne ; Deswarte, Caroline ; Nieto-Patlán, Alejandro ; Surace, Laura ; Kerner, Gaspard ; Itan, Yuval ; Jovic, Sandra ; Avery, Danielle T. ; Wong, Natalie ; Rao, Geetha ; Patin, Etienne ; Okada, Satoshi ; Bigio, Benedetta ; Boisson, Bertrand ; Rapaport, Franck ; Seeleuthner, Yoann ; Schmidt, Monika ; Ikinciogullari, Aydan ; Dogu, Figen ; Tanir, Gonul ; Tabarsi, Payam ; Bloursaz, Mohammed Reza ; Joseph, Julia K. ; Heer, Avneet ; Kong, Xiao-Fei ; Migaud, Mélanie ; Lazarov, Tomi ; Geissmann, Frédéric ; Fleckenstein, Bernhard ; Lindestam Arlehamn, Cecilia ; Sette, Alessandro ; Puel, Anne ; Emile, Jean-François ; Vosse, Esther van de ; Quintana-Murci, Lluis ; Di Santo, James P. ; Abel, Laurent ; Boisson-Dupuis, Stéphanie ; Bustamante, Jacinta ; Tangye, Stuart G. ; Sallusto, Federica ; Casanova, Jean-Laurent

In: Science Immunology, 2018, vol. 3, no. 30, p. eaau6759

Hundreds of patients with autosomal recessive, complete IL-12p40 or IL-12Rß1 deficiency have been diagnosed over the last 20 years. They typically suffer from invasive mycobacteriosis and, occasionally, from mucocutaneous candidiasis. Susceptibility to these infections is thought to be due to impairments of IL- 12–dependent IFN-? immunity and IL-23–dependent IL-17A/IL-17F immunity,...