Thymic hormonal activity on human peripheral blood lymphocytes, in vitro. V. Effect on induction of lymphocytotoxicity

Thymic hormonal effect on lymphocytotoxicity induced in vitro and its target specificity were tested using peripheral blood mononuclear cells (PBMC) of healthy subjects. PBMC were treated by the thymic extract TP-1, a similarly prepared spleen extract (SE) or medium only (1 h, 37 degrees C) and then induced to express cytotoxic activity by exposure to allogeneic tumor cells in mixed cultures or by Con A stimulation. The cytotoxicity developed after several days in culture was assayed on 51Cr labelled tumor cells. TP-1 caused a significant mean enhancement of cytotoxicity induced and assayed on Raji lymphoma cells (mean % specific lysis, 31.5 +/- 2.9 without TP-1 and 53.7 +/- 3.6 with TP-1; n = 42; p less than 0.01). The scatter of individual responses to TP-1 was wide, however, and included also some cases of TP-1 induced suppression. Similar wide scatter of TP-1 effects with emphasis on TP-1 induced enhancement was observed with other tumor cell lines or with Con A as inducers. Usually, SE had no effect on induced cytotoxicity. Target selectivity (specificity) of induced cytotoxicity was tested by induction and assay on several tumor cell lines with crossing over, as well as by cold competition assay. When target selectivity was present, it was not masked by TP-1 induced enhancement. Moreover, in some cases, target selectivity became more pronounced after TP-1 treatment. However, TP-1 enhanced also Con A induced non-specific cytotoxicity. No effect of TP-1 on natural killer cell activity of fresh PBMC could be demonstrated. It is suggested that both selective cytotoxicity (T-cell dependent) and non-selective one maybe modulated directly by TP-1 and indirectly by TP-1 modified secondary interactions in culture. This profound regulatory effects could be demonstrated in the PBMC of immune-intact healthy adults.