ACCUMULATION OF GAMMA DELTA T-CELLS IN HUMAN DYSGERMINOMA AND SEMINOMA - ROLES IN AUTOLOGOUS TUMOR KILLING AND GRANULOMA-FORMATION/

The precise biological function of a subset of T cells bearing gamma/d elta T cell receptor (TCR) remains poorly understood. The present stud y demonstrated the presence of gamma/delta T cells in tumor-infiltrati ng lymphocytes (TIL) and peripheral blood lymphocytes (PBL) of human p atients with dysgerminoma and seminoma when determined by flow cytomet ry and in situ immunohistochemical staining. TIL contained a high perc entage of gamma/delta T cells, ranging from 17.3 to 35.1%. gamma/delta T cells often accumulated within the granulomatous inflammation of tu mor tissues. The majority of gamma/delta T cells were V gamma 9/V delt a 2+ cells. Freshly isolated PBL, TIL and purified gamma/delta T cells showed autologous tumor killing (ATK) activity, which could be inhibi ted by monoclonal antibodies (mAb) against V delta 2. Furthermore, two gamma/delta T cell clones established from TIL showed cytotoxicity ag ainst autologous and allogeneic dysgerminoma, while they had low or no lytic effects on other cell types including carcinomas of ovary and t umor cell lines such as K562, Daudi and Molt-4. Lysis of autologous tu mor cells by the clone was inhibited completely by anti-V delta 2 mAb and partially by mAb against CD3, LFA-1 alpha and ICAM-1 molecules, wh ile it was resistant to anti-CD8, anti-HLA-ABC and anti-HLA-DR mAb. Su pernatants produced by gamma/delta T cell clones induced adhesion, agg regation and increased DNA synthesis of monocytes and some characteris tics of activated macrophages or epithelioid cells. Tumor necrosis fac tor (TNF)-alpha, granulocyte-macrophage colony stimulating factor (GM- CSF) and interferon (IFN)-gamma I were detected in the supernatants of gamma/delta T cell clone. These results suggest that gamma/delta T ce lls accumulating in dysgerminoma and seminoma exhibit ATK activity thr ough V gamma 9/delta 2 TCR and these gamma/delta T cells also play a r ole in the formation of granulomatous inflammation, which is associate d with human dysgerminoma and seminoma.