title: Engagement of NKp30 on Vδ1 T cells induces the production of CCL3, CCL4, and CCL5 and suppresses HIV-1 replication.
abstract: Natural cytotoxicity receptors (NCRs) were originally identified as specific natural killer cell activating receptors that, on binding to their endogenous ligands, trigger the killing of tumor cell targets. We recently described the differentiation of a novel subset of NCR(+) Vδ1 T cells characterized by a remarkably high cytolytic potential against cancer cells. Here we demonstrate that the engagement of NKp30, one of the NCRs expressed de novo on Vδ1 T cells after stimulation, triggers the production of high levels of CCL3/MIP-1α, CCL4/ MIP-1β, and CCL5/RANTES but not of CXCL12/SDF-1. In turn, this NKp30-induced secretion of cc-chemokines is able to significantly suppress the replication of a CCR5 tropic strain of HIV-1 in CD4(+)/CCR5(+) infected PM1 cell lines. This experimental evidence disclosing an unanticipated antiviral function of NCR(+) Vδ1 T cells opens new avenues for understanding the pathogenic role and for manipulating the function of γδ T cells in HIV-1 infection.
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Clinico Humanitas, Via Alessandro Manzoni 113, Rozzano, Milan, Italy.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hudspeth
authors.forename: Manuela
authors.initials: M
authors.lastname: Fogli
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Correia
authors.forename: Joanna
authors.initials: J
authors.lastname: Mikulak
authors.forename: Alessandra
authors.initials: A
authors.lastname: Roberto
authors.forename: Silvia
authors.initials: S
authors.lastname: Della Bella
authors.forename: Bruno
authors.initials: B
authors.lastname: Silva-Santos
authors.forename: Domenico
authors.initials: D
authors.lastname: Mavilio
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000276:immunology / Q000378:metabolism*; D054407:Chemokine CCL4 / Q000276:immunology / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000276:immunology*
chemical_list: C515429:CCL3 protein, human; C066507:CCL4 protein, human; C483024:CCL5 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D016692:Receptors, Antigen, T-Cell, gamma-delta