Cells expressing HTLV-1 genes, Tax and HBZ, showed different patterns of cytolysis by human gd T cells and NK cells

RUGGIERI, M; KOCK, S; BERINI, C; MARIA FLORENCIA QUIROGA; GONZALEZ POLO, V; BIGLIONE, M; FISCH, P

Congreso; 19th International Conference on Human Retrovirology; 2019

Introduction:the most important HTLV-1 viral proteins, HBZ and Tax, regulate not only viral replication but also cell cycle. Human γδ Tcells represent 1 to 5% of the peripheral blood lymphocytes,with Vγ9/Vδ2 T cells as the most abundant subset.The majority of them are activated in an HLA-independentmanner. Vγ9/Vδ2 activation is achieved after binding ofphosphoantigens to the intracellular part of butyrophilintransmembrane molecules.Objective:to determine if HBZ and Tax, expressed by target cells, modulate the cytolitic capacity of human γδ T cells and butyrophilin expression.Methods:β2M FO-1 (melanoma cell line), Myla (CD4+ lymphoid cell line)and Peer (lymphoid cell line) were transduced withconstructs encoding the genes HBZ, Tax or both (H-T) andused as target cells. Cloned Vγ9/Vδ2 T cells and polyclonalγδ T cells served as effector cells and natural killer (NK) cellsas controls. Cytotoxicity was measured by Cr-51 releaseassays. Butyrophilin expression was determined by flowcytometry using the monoclonal antibody 103.2.Results:β2M FO-1 cells expressing HBZ, Tax or H-T genes presentedhigher cytolysis by Vγ9/Vδ2 clones and expanded γδ T cellscompared to control. In contrast, β2M FO-1 cells wereprotected from cytolysis by NK cells when they expressedTax or H-T, compared to HBZ or control. Furthermore, transduction of β2M FO-1 cells with HBZ, but not with Tax or H-Tslightly decreased surface butyrophilin expression,compared to control.Myla cytolysis by expanded γδ T cells was increased onlywhen expressing H-T and, contrary to the cell line β2M FO-1,cytolysis by NK was enhanced when expressing Tax or H-T.Moreover, transfected Peer did not showed differences incytotoxicity by γδ T cells or NK compared with control.Strikingly, a significant difference in IFN-α release wasobserved when NK cells were co-cultured with Myla transfected with HBZ, Tax and H-T.