Selective lysis of the autologous tumor by delta TCS1+ gamma/delta+ tumor-infiltrating lymphocytes from human lung carcinomas.
Two distinct non-overlapping populations of TcR1+ (gamma/delta) T cells have been described: the first, bearing the disulfide-linked gamma/delta heterodimer, is predominant in the peripheral blood; the second, expressing the non-disulfide-linked form of TcR1, is mostly confined to epithelial tissues (lung, gut, skin). TcR1+ lymphocytes may be cytotoxic and could be involved in anti-tumor immunity, especially against tumors at epithelial sites. Freshly derived tumor-infiltrating lymphocytes (TIL) obtained from two patients with lung cancer were enriched in CD3+WT31- cells. The percentage of this subset substantially increased upon culture in the presence of interleukin 2. These cells were TcR1+ as demonstrated by immunofluorescence and immunoprecipitation. In one case only 40% of this population reacted with delta TCS1 mAb, that recognizes the non-disulfide-linked form of TcR1, and co-expressed the CD8 antigen. Cultured TcR1+ TIL were able to kill fresh autologous tumor cells, K-562 and, to a lesser extent, some natural killer-resistant cell lines and allogeneic lung tumor cells in 4-h 51Cr-release cytotoxicity assays. The fractionated delta TCS1+ TIL lysed only autologous tumor cells and K-562, whereas the lytic activity against all the other targets was confined to the delta TCS1- subset. Moreover, the autotumor cytotoxicity was inhibited by anti-HLA class I but not by anti-CD1c or anti-LFA-1 mAb, suggesting that killing of the autologous tumor cells and non-major histocompatibility complex-restricted cytotoxicity are mediated by different mechanisms.
Istituto Scientifico San Raffaele, Milan, Italy.
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Zocchi
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Ferrarini
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Rugarli
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1; D000943:Antigens, Differentiation / Q000276:immunology; D002277:Carcinoma / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D011233:Precipitin Tests; D011948:Receptors, Antigen, T-Cell / Q000145:classification / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018949:Antigens, CD1; D000943:Antigens, Differentiation; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell