chemokine receptors; T helper subsets; memory T cell subsets; TCR repertoire; cytokine plasticity; T lymphocytes
Latorre Daniela, Kallweit Ulf, Armentani Eric, Foglierini Mathilde, Mele Federico, Cassotta Antonino, Jovic Sandra, Jarrossay David, Mathis Johannes, Zellini Francesco, Becher Burkhard, Lanzavecchia Antonio, Khatami Ramin, Manconi Mauro, Tafti Mehdi, Bassetti Claudio L., Sallusto Federica (2018), T cells in patients with narcolepsy target self-antigens of hypocretin neurons, in Nature
, 562(7725), 63-68.
Aschenbrenner Dominik, Foglierini Mathilde, Jarrossay David, Hu Dan, Weiner Howard L., Kuchroo Vijay K., Lanzavecchia Antonio, Notarbartolo Samuele, Sallusto Federica (2018), An immunoregulatory and tissue-residency program modulated by c-MAF in human TH17 cells, in Nature Immunology
, 19(10), 1126-1136.
Geiger Roger, Rieckmann Jan C., Wolf Tobias, Basso Camilla, Feng Yuehan, Fuhrer Tobias, Kogadeeva Maria, Picotti Paola, Meissner Felix, Mann Matthias, Zamboni Nicola, Sallusto Federica, Lanzavecchia Antonio (2016), L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity, in Cell
, 167(3), 829-842.e13.
Sallusto Federica (2016), Heterogeneity of Human CD4(+) T Cells Against Microbes., in Annual review of immunology
, 34, 317-34.
Trautwein-Weidner Kerstin, Gladiator André, Kirchner Florian R, Becattini Simone, Rülicke Thomas, Sallusto Federica, LeibundGut-Landmann Salomé (2015), Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis., in PLoS pathogens
, 11(10), 1005164-1005164.
Mele Federico, Basso Camilla, Leoni Cristina, Aschenbrenner Dominik, Becattini Simone, Latorre Daniela, Lanzavecchia Antonio, Sallusto Federica, Monticelli Silvia (2015), ERK phosphorylation and miR-181a expression modulate activation of human memory TH17 cells., in Nature communications
, 6, 6431-6431.
Okada Satoshi, Markle Janet G, Deenick Elissa K, Mele Federico, Averbuch Dina, Lagos Macarena, Alzahrani Mohammed, Al-Muhsen Saleh, Halwani Rabih, Ma Cindy S, Wong Natalie, Soudais Claire, Henderson Lauren A, Marzouqa Hiyam, Shamma Jamal, Gonzalez Marcela, Martinez-Barricarte Rubén, Okada Chizuru, Avery Danielle T, Latorre Daniela, Deswarte Caroline, Jabot-Hanin Fabienne, Torrado Egidio, Fountain Jeffrey, Belkadi Aziz (2015), IMMUNODEFICIENCIES. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations., in Science (New York, N.Y.)
, 349(6248), 606-13.
Becattini Simone, Latorre Daniela, Mele Federico, Foglierini Mathilde, De Gregorio Corinne, Cassotta Antonino, Fernandez Blanca, Kelderman Sander, Schumacher Ton N, Corti Davide, Lanzavecchia Antonio, Sallusto Federica (2015), T cell immunity. Functional heterogeneity of human memory CD4⁺ T cell clones primed by pathogens or vaccines., in Science (New York, N.Y.)
, 347(6220), 400-6.
The effectiveness and robustness of the immune response is dependent on different types of effector and memory T cells capable of migrating to different tissues and of producing a variety of cytokines in response to diverse types of pathogens. In principle this response could be built on: i) multiple clones, each performing a given function; ii) multiple functions performed by distinct descendants of a single clone; or, iii) any combination of the two. For this reason, understanding the distribution of antigen-specific T cell clones within effector and memory subsets is of both fundamental and practical importance. This proposal is centered on fundamental questions that pertain to T lymphocyte functions in protection and pathology. We aim at defining the lineage relationship between different memory T cell subsets and between T helper cells with polarized or mixed cytokine profiles, and the natural and therapeutic plasticity of effector and memory T cells at different stages of differentiation. The proposal builds on our knowledge of human T cell differentiation and on the identification of different types of effector and memory T cell subsets, as well as on our early studies on the epigenetic control of human CD4 T cell polarization and plasticity. We will take advantage of multiparametric flow cytometry and cell sorting, high throughput T cell cloning, and next generation sequencing to analyse the human antigen-specific immune response at the clonal level. The project is organized in two main subprojects. The first will address the distribution of memory and effector T cells within individual expanded clones of antigen-specific T cells primed in vivo by different classes of antigens. We will establish, at the clonal level, the lineage relationship of effector and memory T cell subsets, such as T cells producing IFN-?, IL-4, IL-17 and IL-22, alone or in different combinations, or circulating follicular helper T cells and central memory and effector memory T cells. The second subproject will address at the molecular level the mechanisms of T cell differentiation and plasticity that control expression of effector cytokines. The hypotheses tested are strongly supported by preliminary observations from our own laboratory as well as from the biomedical literature. We expect that these studies will significantly expand our basic understanding of T cell biology and will have translational implications for vaccination and immunotherapy.