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In the hemato-lymphoid system, a vast majority of T cells (Ͼ90%) express antigen receptors composed of clonally variable alpha beta (␣␤) heterodimers in association with the invariant components of the CD3 complex, while a small population of T cells (Ͻ10%) express the gamma delta (␥␦) T-cell receptor (TCR) (Kabelitz, 1992).Among the known ligands for ␥␦ T cells, heat shock proteins (hsps) and phospholigands have gained particular importance because of their wide distribution and oligoclonal stimulation of ␥␦ T cells (Kaufmann, 1996). The hsps are ubiquitous and highly conserved proteins expressed at elevated levels under stress (Kaufmann, 1990). It has been suggested that the focus of ␥␦ T cells on hsps would promote a rapid response to cell stress caused by a variety of insults, including infection, inflammation and neoplastic transformation. Evidence for the role of hsp molecules in tumor cell recognition by ␥␦ T cells has been accumulating. Over-expression of hsp27 achieved by transfection in the breast carcinoma-derived cell line MCF-7 made it susceptible to ␥␦ T-cell killing, whereas cytotoxicity mediated by NK or LAK cells was not increased (Mahvi et al., 1993). The Burkitt's lymphoma cell line Daudi is known to selectively activate V␥9/V␦2 T cells. It was further demonstrated that the reactivity of ␥␦ T cells toward Daudi tumor cells could be inhibited by anti-hsp60 antibodies Fisch et al., 1990;Kaur et al., 1993). In lung carcinomas, where large numbers of ␥␦ T cells have been localized, overexpression of hsp72 was observed (Ferrarini et al., 1994).The present investigations were focused on understanding the potential involvement of the peripheral blood ␥␦ T cells in immune responses to oral squamous cell carcinoma. The ␥␦ T cells were expanded from the peripheral blood of oral cancer patients by co-culturing peripheral blood lymphocytes (PBLs) with Daudi Burkitt's lymphoma cells. The expanded cell population contained a major population of ␥␦ T cells expressing the V␥9 and V␦2 receptors. These ␥␦ T cells exhibited increased cytotoxicity against Daudi and oral tumor cells compared with other tumor targets. Monoclonal antibodies (MAbs) to hsp60 inhibited the cytotoxicity of ␥␦ T cells against both tumor targets, suggesting that hsp60 molecules expressed on the oral tumor cells serve as possible ligands for the ␥␦ T cells. MATERIAL AND METHODS PatientsBlood samples were collected from oral cancer patients (n ϭ 10) with clinically and histologically proven squamous cell carcinoma staged according to the TNM system of UICC (3rd ed.). Tumor biopsies were obtained from a separate set of oral cancer patients undergoing surgery. None of the patients had received chemotherapy, radiotherapy or immunotherapy before surgery. MAbsThe following antibodies were used. TCR␦1 (anti-TCR␥␦), BMA 031(anti-TCR␣␤), Ti␥A (anti-V␥9), BB3 (anti-V␦2) and 23D12 (anti-V␥2/3/4) were obtained as gifts from Dr. D. Kabelitz (Langen, Germany) and Dr. R.L.H. Bolhuis (Rotterdam, The Netherlands and 4A11 (anti V␥4) was obtained as a gift f...

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