REGULATORY CELLULAR INTERACTIONS IN THE PRIMARY MIXED LYMPHOCYTE-REACTION

Limiting dilution analysis (LDA) of allogeneic and syngeneic murine mi xed lymphocyte reactions was used to study the heterogeneity both of t he responding spleen cells and of the stimulating antigen-presenting d endritic cells (DC). In contrast with traditional LDA of single-hit pr ocesses, a non-linear dependence of the proportion of negative microcu ltures on responding spleen cell concentration was obtained. The non-l inearity of this LDA plot was interpreted as being the result of a com petitive interaction between two types of limiting precursor cells. Th e regulatory and stimulatory functions of DC were investigated in the same LDA systems by testing various levels of DC from spleen or thymus as limiting cells in the presence of a constant quantity of syngeneic splenic responder T cells. This revealed a functional heterogeneity a mongst DC, which were found to suppress proliferation of responder cel ls at low DC levels but to stimulate proliferation at higher levels. A t levels where splenic DC became stimulatory, thymic DC remained suppr essive.