Cellular basis for adriamycin-induced augmentation of cell-mediated cytotoxicity in culture.

The cellular basis for the augmented cell-mediated cytotoxic (CMC) response seen when spleen cells from Adriamycin (ADM)-treated mice were stimulated in culture was investigated. Under conditions where mature macrophages were reduced (adherent or silica-sensitive cells removed) at time of alloantigen challenge, the cells from ADM-treated mice developed levels of CMC activity much higher than the low levels which were developed by similar subsets of cells from nontreated control mice. This indicates that ADM treatment enriched a subset of cells in spleen which was nonadherent, silica-insensitive, and nonphagocytic but was capable of providing accessory function. When mature macrophages were not removed, the capability to develop an augmented level of CMC was shown to be associated with a subset of cells from ADM-treated mice which was adherent to either plastic or nylon wool. In recombination experiments, it was found that the removal of Thy 1.2+ cells from the adherent subset from ADM-treated mice had little effect on the response, while their removal from the adherent subset from nontreated mice resulted in elevated levels of response. A similar effect was obtained when Lyt 2.2+ cells were eliminated but not when Lyt 1.2+ cells were removed. This indicates that a Thy 1.2+, Lyt 1-2+ cell, involved in regulation of the response, was missing from or failed to function in the ADM-treated population. Based on these findings, ADM apparently induces modifications in two cell subsets: (a) immature cells of the monocyte/macrophage lineage which can provide accessory function; and (b) adherent, Lyt 2+ T-cells which cooperate in maintaining levels of CMC activity at "normal" levels.