RNA VIRUS PERSISTENCE MEETING: MECHANISMS AND CONSEQUENCES

KOCK; FISCH P; MYSCHKIN E; BIGLIONE M; RUGGIERI M

Congreso; RNA VIRUS PERSISTENCE MEETING: MECHANISMS AND CONSEQUENCES; 2018

Objectives: The aim of this study is to determine if expression of HTLV-1 proteins HBZ and Tax by target cells changes MHC unrestricted cytolysis by human γδ T cells and affects butyrophilin expression. Methods: Cytotoxicity was measured by Cr-51 release assays. β2M FO-1 melanoma cells were transduced with expression constructs encoding the viral proteins HBZ, Tax or both (H-T) and used as target cells. Cloned Vγ9/Vδ2 T cells and polyclonal γδ T cells served as effector cells and cloned natural killer (NK) cells as controls. Butyrophilin expression was measured by flow cytometry and using the monoclonal antibody 103.2. Results: Vγ9/Vδ2 clones and expanded γδ T cells showed increased cytolysis of β2M FO-1 cells expressing HBZ, Tax or H-T genes as compared to mock. In contrast, β2M FO-1 cells were protected from cytolysis by NK cells when they expressed Tax, compared to HBZ or mock. Furthermore, transduction by Tax or HBZ of β2M FO-1 cells did not have an effect on surface butyrophilin expression. Conclusions: Cytolysis by human Vγ9/Vδ2 T cells was increased following expression of HTLV-1 genes Tax and HBZ by target cells without BTN3A upregulation. Thus, Vγ9/Vδ2 T cells might play a role in the immunosurveillance against HTLV-1 virus. This finding may be linked to our observation by cDNA spectratyping that Vγ9/Vδ2 T cells are decreased in HTLV-1 infected donors. In contrast, Tax may protect target cells from NK-mediated lysis which could be a new mechanism of the virus to escape NK-mediated immunity