Analysis of anti-tumour and anti-viral reactivities of human gamma-delta T cells

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Authors

KNIGHT Andrea PISKÁČEK Martin KRÁLOVÁ Romana KRCHNIAKOVÁ Mária GALLOVÁ Petra KUBEŠ Martin RIHOVA Lucie VSIANSKA Pavla PACASOVA Rita PENKA Miroslav ADAM Zdenek POUR Ludek HAJEK Roman VAŠKŮ Anna

Year of publication 2016
Type Appeared in Conference without Proceedings
MU Faculty or unit

Faculty of Medicine

Citation
Description Human gd T cells are currently the subject of intensive research ana large expansions of tumour-reactive gd T cells have been observed inpatients with haematological malignancies including Multiple Myeloma (MM) and chronic leukaemias (CML, CLL) in our laboratory. However, the role of innate effector gd T cells subsets in patients progressing from monoclonal gammopathy of undetermined significance (MGUS) to MM is currently unknown. Previously, we have also shown expansion of gd T lymphocytes in cytomegalovirus (CMV) seropositive healthy donors compared to CMV seronegative individuals (p=0.0002) suggesting their direct involvement in anti-CMV immune response. Here we performed detailed analyses of expansion, phenotype, clonality and function of Vdl and Vd2 gd T cells isolated from patients and age-matched healthy donors (HD, n=53). We have analysed bone marrow (BM) and paired peripheral blood (PB) samples from MGUS (n=30) and newly diagnosed myeloma (n=52) patients. Second, we determined the whole genome profiles of tumour-reactive gd T cells and compared these to healthy donors. Third, we analysed healthy donors with five most commonly presented aileles for anti-CMV responses of gd T cells in parallel to CMV-specific ab T cells in the same HLA-A*02, HLA-A*01, HLA-A*24, HLA-A*07, and HLA-A*35 donors. The microRNA (miRNA) expression profiles have been generated from HLA-A*02, HLA-A801 CMV seropositive HD. Fourth, detailed analyses of the TCR repertoire of the gamma (g1-8, g9, g10, g11) and delta (d1-d8) chains have been determined in HD and patient cohorts. The summary of results will be presented and discussed.
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