gdT cells recognize target cells expressing Human T cell lymphotropic virus type 1 (HTLV-1) genes Tax and HBZ.

FISCH PAUL; RUGGIERI MATÍAS; BIGLIONE MIRNA

Conferencia; International Conference on Immunology, Immunodeficiency and Immunotherapy; 2018

Introduction: HTLV-1 is an oncoretrovirus that infects approximately 10 million individuals worldwide. Five percent will develop either HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or Adult T-cell Leukemia/Limphoma (ATLL), for which there are still no effective treatments. The HTLV-1 viral protein HBZ and Tax, the most important viral proteins, regulate not only viral replication but also cell cycle. Human γδ T cells 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-independent manner. Vγ9/Vδ2 activation depends on phosphoantigens that bind to the intracellular part of butyrophilin transmembrane molecules.Objectives: to determine if γδ T cells can kill cells expressing HBZ and Tax and whether these might regulate butyrophilin expression.Methods: Cr-51 release assays were employed to measure γδ T cell cytotoxicity. β2M FO-1 melanoma cells were transduced with the sequence encoding the genes for proteins HBZ, Tax or both (H-T) and used as target cells. Vγ9/Vδ2 T cells from clones, as well as polyclonal γδ T cells expanded with either zoledronate or Con A served as effectors. Butyrophilin expression was measured by flow cytometry and using mAb 103.2 (C. Harly et al. 2012).Results: Vγ9/Vδ2 clones and expanded γδ T cells show increased MHC unrestricted cytolysis of β2M FO-1 cells retrovirally transduced by HBZ, Tax or H-T genes, compared to mock. Expression of both proteins, made the β2M FO-1 target cells more susceptible to γδ mediated lysis than expression of Tax or HBZ alone. Transduction by Tax and HBZ of β2M FO-1 cells did not have an effect on surface butyrophilin expression.Conclusions: we present initial evidence that cytolysis by human Vγ9/Vδ2 T cells increased following expression by target cells of Tax and HBZ. This mechanism is likely not related to an upregulation of surface butyrophilins.