Conditional requirement for accessory cells in the response of T cells to Con A.

The response to Concanavalin A (Con A) of unseparated lymph node cells and of T cells isolated from them has been studied over a mitogen dose range of 0.2 microgram to 16 micrograms/ml. Accessory cell depleted T cells respond only to high doses of Con A and then only weakly. The magnitude (proliferative activity) of the response as well as the sensitivity to the mitogen can be modified by accessory cells (AC), lymphokines and by chemical modification of cell surface glycoproteins. Accessory cell function can be inhibited by antibodies directed against cell surface molecules on accessory cells (Ia) or on T cells (L3T4). Changes in the mitogen sensitivity of the response are not necessarily associated with changes in the magnitude of the response. The mitogen sensitivity can be decreased with anti-Ia antibody and can be increased by treatment with IL-l and/or interferon gamma (IFN-). We postulate that the increase in sensitivity to Con A is a function of the density of cell surface molecules with which T and AC cells interact. The magnitude of the response is primarily determined by the frequency of AC in culture; it decreases as the number of AC is reduced and increases as AC are added to the cultures. Mitogen sensitivity is a new tool for the analysis of nonspecific T cell activation. Our data bring the accessory cell requirement for mitogen activation of T cells into a new perspective: AC--or factors produced by them--are essential when low (1-2 micrograms/ml Con A) doses are used and are less or not at all necessary when high doses (6-10 micrograms/ml) of mitogen are applied.