title: Human Cytotoxic T Lymphocytes Form Dysfunctional Immune Synapses with B Cells Characterized by Non-Polarized Lytic Granule Release.
abstract: Suppression of the cytotoxic T cell (CTL) immune response has been proposed as one mechanism for immune evasion in cancer. In this study, we have explored the underlying basis for CTL suppression in the context of B cell malignancies. We document that human B cells have an intrinsic ability to resist killing by freshly isolated cytotoxic T cells (CTLs), but are susceptible to lysis by IL-2 activated CTL blasts and CTLs isolated from immunotherapy-treated patients with chronic lymphocytic leukemia (CLL). Impaired killing was associated with the formation of dysfunctional non-lytic immune synapses characterized by the presence of defective linker for activation of T cells (LAT) signaling and non-polarized release of the lytic granules transported by ADP-ribosylation factor-like protein 8 (Arl8). We propose that non-lytic degranulation of CTLs are a key regulatory mechanism of evasion through which B cells may interfere with the formation of functional immune synapses by CTLs.
authors.affiliation: Department of Life Sciences, University of Siena, via Aldo Moro 2, Siena 53100, Italy. Electronic address: anna.kabanova@unisi.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Kabanova
authors.affiliation: Department of Life Sciences, University of Siena, via Aldo Moro 2, Siena 53100, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sanseviero
authors.affiliation: Hematology Unit, University of Siena, viale Bracci 16, Siena 53100, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Candi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, via Aldo Moro 2, Siena 53100, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gamberucci
authors.affiliation: Hematology Unit, University of Siena, viale Bracci 16, Siena 53100, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gozzetti
authors.affiliation: Department of Immune Haematology and Transfusion Medicine, University Hospital of Siena, viale Bracci 16, Siena 53100, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campoccia
authors.affiliation: Hematology Unit, University of Siena, viale Bracci 16, Siena 53100, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Bocchia
authors.affiliation: Department of Life Sciences, University of Siena, via Aldo Moro 2, Siena 53100, Italy.
authors.forename: Cosima Tatiana
authors.initials: CT
authors.lastname: Baldari
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005089:Exocytosis; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000075745:rab27 GTP-Binding Proteins
chemical_list: D000075745:rab27 GTP-Binding Proteins; C066694:RAB27A protein, human; C477339:ARL5B protein, human; D020727:ADP-Ribosylation Factors; D020691:rab GTP-Binding Proteins