Suppression of T-cell response in autologous mixed lymphocyte-tumor culture by large granular lymphocytes.
The role of large granular lymphocytes (LGL) in the autologous mixed lymphocyte-tumor culture (MLTC) was studied in cancer patients with malignant pleural effusions. When blood lymphocytes were cocultured in vitro with autologous tumor cells freshly isolated from carcinomatous pleural effusions, [3H]thymidine incorporation was weakly stimulated on day 6 in 6 of 30 samples. Removal of LGL from the responder population by treatment with the Leu-7 or Leu-11b monoclonal antibody plus complement (C') induced or augmented the proliferative response. LGL and small T-lymphocytes were isolated by discontinuous Percoll gradient centrifugation and tested separately for the proliferative response to autologous tumor. T-cells proliferated in 24 of 30 cases, while LGL showed no proliferation. Addition of LGL to autologous mixed T-cell-tumor cultures suppressed the proliferation of T-cells. LGL, however, did not inhibit T-cell proliferation induced by alloantigens and lectins. The suppressive activity of Percoll-purified LGL was not reduced by OKT3 plus C' treatment, but it was totally abrogated by Leu-11b plus C'. Supernatants produced by 24-hour culture of LGL with autologous tumor contained soluble factors that suppressed the autologous MLTC without killing the autologous tumor or T-blasts. The LGL-mediated suppression was not abolished by anti-interferon-alpha or anti-interferon-gamma antibody. Activation of T-cells in the autologous MLTC induced lytic potential restricted to autologous tumor. In the presence of LGL, T-cells failed to develop autotumor killing activity. Once autotumor killer T-cells were generated in autologous MLTC, their cytotoxicity was no longer inhibited by LGL. These results indicate that LGL from patients with carcinomatous pleural effusions suppress the capacity of autotumor-recognizing T-lymphocytes to proliferate and develop autotumor cytotoxicity in the autologous MLTC. This could explain why fresh T-cells have no cytolytic activity to autologous tumor.
Uchida
A
A
Klein
E
E
D000230:Adenocarcinoma / Q000276:immunology; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007372:Interferons / Q000276:immunology / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology*; D010996:Pleural Effusion / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000906:Antibodies; D004247:DNA; D007372:Interferons