A quantitative analysis of antigen-triggered lymphokine production by activated T cells.

We have developed a theoretical model to describe the triggering of lymphokine release from antigen-specific, activated T (T') cells, and we have used this model to define parameters that regulate this interaction. Under assay conditions of T' cell excess, the efficiency of triggering is a function of the target cell type. When various H-2k-bearing target cells were used to trigger B10.AQR T' cells activated against B10.A cells (anti-Kk), a hierarchy of triggering efficiency was observed with B10.A Con A blasts greater than R1.1 tumor cells greater than B10.A spleen cells greater than B10.A lymph node cells. There was a 10-fold difference in triggering efficiency between Con A blasts and lymph node cells. A similar pattern of reactivity was observed for various H-2d-bearing target cells used to trigger CBA T' cells specific for BALB/c antigens (anti-H-2d). Under assay conditions of T' cell excess, the order of reaction, i.e., the number of target cells per T' cell required to trigger lymphokine release, remained constant for the different target cell types. However, the order of reaction can vary with conditions of T cell activation. CBA T' cells activated against BALB/c spleen cells exhibited pseudo-first-order reactivity when triggered for lymphokine release with P815 target cells, whereas CBA T' cells activated against UV-irradiated P815 cells exhibited pseudo-second-order reactivity when triggered by the same tumor cells. Thus, T cells with the same apparent specificity can be qualitatively different in their reactivity with antigen. Under assay conditions of target cell excess, our analysis indicated that no T-T interaction was involved in the triggering reaction. Finally, our analysis was applied to study the nature of cross-reactivity. The results indicated that the triggering of lymphokine elicited by a cross-reactive antigen was due to the reactivity of a discrete subset of T' cells.