Activation of autoreactive cytolytic T lymphocyte clone against human melanoma by anti-T3 monoclonal antibody and autologous accessory cells.
A cytotoxic T-lymphocyte (CTL) clone Tc1.8 was derived in a limiting dilution culture from a single cell that was derived from melanoma-involved lymph node lymphocytes activated in in vitro coculture against the autologous melanoma cells (VIP). The clone Tc1.8 (T3+, T8+, T4-, and Leu7-) expressed restricted cytolytic activity against only the autologous target VIP. As it aged in continuous culture containing interleukin 2, Tc1.8 lost cytolytic activity. The cytolytic function could be restored, however, with monoclonal antibody (MoAb) against T3 (OKT3) or with F(ab')2 fractions of OKT3, and upon restimulation with irradiated accessory cells. OKT3-mediated reinduction of cytotoxicity by the aged Tc1.8 could not be achieved if the T3 molecules were modulated from the effector cell surface following overnight incubation of Tc1.8 with saturating concentrations of OKT3 MoAb. Following reactivation with OKT3 Tc1.8 gained cytolytic function against NK targets in addition to VIP. Reactivation with F(ab')2 fractions of OKT3 and with autologous accessory cells, however, maintained its restricted antigen fidelity. The NK-like activity of Tc1.8 upon reactivation with OKT3 resulted from conjugate formation between the activated Tc1.8 and NK targets via the activating ligand itself. Thus, upon stimulation with anti-T3 MoAb and with autologous accessory cells, independently, the autoreactivity could be restored in an aged and inactive CTL clone.
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D000954:Antigens, Surface