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

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.