In vitro studies of natural and tumor-associated immunity in patients with transitional cell carcinoma of the urinary bladder
Sammanfattning: Peripheral blood lymphocytes (PBL) from patients with transitional cell carcinoma of the urinary bladder (TCC-bladder) were studied using a SlCr-release assay for their in vitro cytotoxicity against a panel of allogeneic tissue culture cell lines of TCC-bladder and other origins. Control PBL were obtained from four different groups of donors. Individual donor's lymphocytes frequently displayed cytotoxicity to any one of the target cells. However, PBL from each of the three TCC-bladder groups had strongly elevated mean cytotoxicity to the TCC-bladder targets as compared to that to the control targets. The control groups did not show this. The mean cytotoxicity of PBL from the TCC bladder groups to the bladder tumor targets was significantly higher than that of the control groups. The results suggest the existence of a disease related reactivity in TCC-bladder superimposed on background of natural cytotoxicity. Effector cell studies in allogeneic lymphocyte/tumor target combinations revealed that the cytotoxic effector cells within all donor groups were indistinguishable from the lymphocytes responsible for antibody-dependent cellular cytotoxicity (ADCC, K-cells). A possible involvement of antibodies in the cytotoxic reactions was studied by adding Fab-fragments of anti-human immunoglobulin antibodies (Fab-alg) to the PBL/target cell mixtures. These reagents inhibited cytotoxicity, although inhibition was usually incomplete. The results suggest the involvement of both antibody dependent and antibody independent mechanisms in the cell-mediated cytotoxicity (CMC) against allogeneic target cells. Investigations of effector cell mechanisms in autologous PBL/tumor target combinations revealed the presence of other mechanisms than seen in most allogeneic combinations. Thus, the effector cells were distinct from K-cells and the reactions were not inhibited by the presence of Fab-alg. The results suggest that these autologous reactions may be mediated by antibody independent cytolytic T-lymphocytes (CTL) and may require HLA-compatibility between effector cells and target cells. However, at the present stage, alternative explanations must also be considered. In the search for humoral antibodies to tumor cells in serum of TCC-bladder patients and controls an ADCC assay was used. To avoid inhibition by blocking factors present in whole serum, IgG-fractions were prepared. ADCC inducing antibodies were found in IgG-fractions from both TCC-bladder patients and controls. However, when tested against one cell line of TCC-bladder origin and one control cell line, the IgG-fractions from TCC-bladder patients were on the average more cytotoxic to the TCC-bladder target than to the control. This was not seen with the IgG-fractions of the controls. This suggests that TCC-bladder patients develop a humoral response related to their disease. However, the nature of the antigen(s), responsible for these reactions remains to be established.
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