A long term human alloimmune cytotoxic T cell line (LFA-1+, T3+, T8+, T11+, T4-) was studied as a model system to investigate the mechanism of inhibition of effector function by several anti-LFA-1 and anti-T8 monoclonal antibodies (MAb). Several anti-LFA-1 MAb, reactive with unique epitopes, by themselves or pooled, inhibited cytolysis 40 to 60% in a 4 hr 51Cr-release assay. Similarly, several anti-T8 MAb blocked lysis by only 30 to 60%. However, when anti-LFA-1 MAb and anti-T8 MAb were pooled, cytolysis was inhibited 70 to 100% and the effective dose of either MAb was decreased 10 to 50 fold. Several other MAb to T cell surfaces structures, when combined with anti-LFA-1, showed no synergistic effects in blocking cytolysis. Ca++ pulse experiments indicated both anti-LFA-1 and anti-T8 blocked lysis during the pre-Ca++ dependent phase. The kinetics of lysis was reversibly inhibited by anti-LFA-1 or anti-T8, but anti-LFA-1 and anti-T8 MAb in combination irreversibly blocked cytolysis. Neither anti-LFA-1 or anti-T8, alone or in combination, modulated its respective surface structure. These results suggest the necessary participation of LFA-1 and T8 structures in the recognition phase of cytolysis. One possibility, suggested by the synergistic effects of anti-LFA-1 and anti-T8 in blocking cytolysis is that a functional linkage between LFA-1 and T8 molecules occurs during the recognition of allogeneic targets by cytotoxic T lymphocytes. Supported by PHS grant No ROI CA 35638 awarded by the NCI, DHHS.
|Original language||English (US)|
|Pages (from-to)||no. 156|
|State||Published - 1984|
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