HLA-B5-restricted auto-tumor-specific cytotoxic T cells generated in mixed lymphocyte-tumor-cell culture.
T-cell-enriched lymphocyte populations derived from the malignant exudate of a patient with ovarian carcinoma were exposed to autologous tumor cells in the mixed lymphocyte-tumor-cell culture (MLTC) and propagated for 42 days. Proliferation of lymphocytes depended on exposures to autologous tumor cells and on the presence of IL-2. After 7 days, the MLTC-lymphocytes lysed K562 and the autologous tumor cells. The latter effect was not inhibited by monoclonal antibodies (MAbs) reactive with MHC class-I antigens or with CD3. After 7 restimulations, the culture was enriched in CD8+ cells (92%) and showed selective lytic activity against the autologous tumor. This function was inhibited by the alpha-class I or alpha-CD3 MAbs, and also by antibodies reactive with the HLA B locus or B5 allele products. The antibodies reactive with HLA A molecules had no such effect. It seems therefore that the function of the CTLs was restricted by HLA B5. Analysis of the TCR beta genes indicated clonal T-cell expansion in this culture. This MLTC was 1 of 21 initiated with 11 blood- and 10 tumor-derived lymphocyte (TIL) populations prepared from the malignant effusions of ovarian carcinoma patients. None of these ex-vivo lymphocytes lysed autologous tumor cells. In 17 MLTCs the lymphocytes did not proliferate, and in 3 cultures the proliferation was maintained only for 2-3 weeks. In 3 of 4 cultures auto-tumor cytotoxicity was induced.
Wang
P
P
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
Végh
Z s
Zs
Vánky
F
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Klein
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D000483:Alleles; D015139:Blotting, Southern; D003602:Cytotoxicity, Immunologic; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D009369:Neoplasms / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006680:HLA Antigens; D015235:HLA-B Antigens; C035270:HLA-B5 antigen