Regulatory influence of dendritic cells on primary mixed lymphocyte reaction

Limiting dilution analysis (LDA) was used to study heterogeneity of both murine splenocytes responding in allo- and auto-MLR, and of stimulating antigen-presenting dendritic cells (DC). In contrast to standard LDA of single-hit processes, a nonlinear dependence of the proportion of negative microcultures on responding spleen cell concentration was obtained (LDA-plot). The nonlinearity of the LDA-plot is interpreted as being the result of a competitive interaction of two types of limiting precursor cells. The accessory function of DC was investigated in the same LDA system, by testing various levels of accessory cells from the spleen or thymus as limiting cells in the presence of a constant quantity of splenocyte responder cells. This revealed a functional heterogeneity among DC which were found to suppress or stimulate proliferation of responder cells depending on DC quantity in culture.